Fetal Alcohol Spectrum Disorders: Concepts, Mechanisms, and Cure

Sushil K. Sharma, Ph.D.
Academic Dean, American International School of Medicine (AISM), Georgetown, Guyana, South America, US Corporate Headquarters, Stone Mountain, Georgia, USA

Series: Neurology – Laboratory and Clinical Research Developments
BISAC: MED056000

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Alcoholism exerts a high genetic as well as epigenetic load and may be regarded as one of the most prevalent, identifiable, and preventable neuropsychiatric illnesses afflicting modern society today. Alcohol constituted 3.2% of all worldwide deaths in the year 2006 and is associated with >60 diseases, including fetal alcohol spectrum disorder (FASD), cancers, cardiovascular diseases, liver cirrhosis, neuropsychiatric disorders and life-threatening injuries.

Fetal alcohol spectrum disorder (FASD) is a collective term representing fetal abnormalities associated with maternal alcohol abuse. FASD is a devastating developmental disorder resulting from alcohol exposure during fetal development. It is a considerable public health problem worldwide and is characterized by CNS abnormalities, dysmorphic facial features, and growth deficiency.

Although it is well-established that intra-uterine alcohol exposure can lead to FASD, characterized by cognitive and behavioral impairments, alcohol abuse is still highly prevalent and contributes to a significant loss of economy and productivity throughout the entire world. Children with FASD become a serious and persistent socioeconomic burden to society, as they require specialized healthcare liabilities throughout their entire lives as a consequence of their parents’ irresponsible drinking behavior.

The primary aim of the inter-disciplinary and integrated genome research network (consisting of molecular biologists, psychopharmacologists, system biologists with mathematicians, human geneticists, and clinicians) is to better understand the genetics and epigenetics of alcohol addiction by identifying candidate genes and molecular mechanisms involved in the etiopathogenesis of FASD, and to provide recommendations to the government and scientific community for global dissemination of emerging knowledge and implementation of FASD interventions.

In Fetal Alcohol Spectrum Disorder: Concepts, Mechanisms, and Cure, the author has presented the novel concept of charnolopharmacology, which plays a crucial role in determining the life and death of the fetus during intrauterine fetal alcohol exposure (FAE). More specifically, it proposes mitochondrial bioenergetics-based charnolopharmacotherapeutics for personalized theranostics of FASD, involving diversified charnolopathies, embryopathies, and infertility; resulting in poor quality of life.

Although several concepts, mechanisms and potential therapies have been proposed recently to overcome the deleterious consequences of FASD, the author has now proposed charnolopharmacotherapeutics, which is based on ethanol-induced compromised mitochondrial bioenergetics and the induction of charnolopathies initially in the spermatocyte and oocyte during the prezygotic phase, and subsequently in the neural progenitor cells (NPCs) during the post-zygotic phase of pregnancy. Hence, drugs inhibiting CB formation and/or augmenting charnolophagy as a basic molecular mechanism of intracellular detoxification during the acute phase, stabilizing charnolophagosome and preventing charnolosome sequestration and budding during chronic phase, will have therapeutic potential in FASD embryopathies, which is elegantly described in this book.

The most unique feature of this book is that it introduces original concepts of mitochondrial bioenergetics, genomics, and epigenomics to successfully manage FASD. Particularly, mitochondrial bioenergetics-based CB prevention/inhibition, charnolophagy induction, and charnolophagosome and charnolosome stabilization are novel therapeutic targets for safe and effective clinical management of FASD. These concepts and mechanisms are based on several years of basic research and original discoveries by the author. (Imprint: Nova Biomedical)

Main Message

Words of Wisdom

Acknowledgement

About this Book

About the Author

Abbreviations

Definitions

Preface

PART I. Introduction

Chapter 1. Alcohol Addiction (Basic Background)

Chapter 2. Global Incidence of Fetal Alcohol Syndrome

Chapter 3. FASD and Loss of Economy and Productivity

Chapter 4. Fetal Alcohol Spectrum Disorder (Historical Perspective and Clinical Symptoms)

Chapter 5. FASD and Other Mental Health Disorders

Part II. Molecular Mechanisms of FASD

Chapter 6. Molecular Mechanisms of FASD

Chapter 7. Conventional and Potential FASD Biomarkers

Chapter 8. Pharmacogenomics of FASD

Chapter 9. Epigenetics of FASD (Part-1)

Chapter 10. Epigenetics of FASD (Part-2)

Chapter 11. Microarray Analyses of FASD

Part III. Basic Concepts of FASD

Chapter 12. Clinical Significance of Charnoly Body (CB) in FASD

Chapter 13. CB Pathogenesis of FASD (A Compromised Charnolophagy in FASD)

Chapter 14. Mitochondrial Bioenergetics of FASD (Recent Update)

Chapter 15. Clinical Significance of Charnolophagy in FASD

Chapter 16. Micro-RNA and FASD

Chapter 17. Clinical Benefits of Animal Models in FASD

Part IV. Recent Experimental Studies on FASD

Chapter 18. In-Vitro Experimental Models of FASD

Chapter 19. Emerging Cellular and Molecular Mechanisms of FASD

Chapter 20. Cerebral Organoids and Cell Culture Studies of FASD

Chapter 21. Emerging Molecular Mechanisms of Neurotoxicity of FASD

Chapter 22. FASD: Recent Update

Part V. FASD Neuroprotection and Treatment

Chapter 23. Molecular Mechanisms of Neuroprotection in FASD

Chapter 24. Fetal Alcohol Spectrum Disorder (FASD) Prevention, Diagnosis, and Treatment

Chapter 25. Prevention and Treatment of FASD (Recent Update)

Index

Preface

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Chabenne, A., Moon, C., Ojo, C., Khogali, A., Nepal, B., Sharma, S. 2015. Biomarkers in Fetal Alcohol Syndrome. Biomarkers and genomic Medicine. 6, 12-22.
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Ramsey, M., 2010.Genetic and epigenetic insights into fetal Alcohol spectrum disorders. Genome Med. 2(4), 27.
Sarkar, D. K. 2016. Male germline transmits fetal Alcohol epigenetic marks for multiple generations: a review. Addict. Biol. 21(1), 23-34.
Sharma S., Rais, A., Sandhu, R., Nel, W., Ebadi, M. 2013. Clinical significance of metallothioneins in cell therapy and nanomedicine.

Int. J. Nanomedicine. 8, 1477-1488.
Sharma, S. 2014. Nanotheranostics in evidence based personalized medicine. Curr. Drug Targets. 15(10), 915-930.
Sharma, S. 2017. Zika Virus Disease (Prevention and Cure). Nova Science Publishers, New York, U.S.A.
Sharma, S. Charnoly Body as Novel Biomarker of Drug Addiction. 4th International Congress & exhibition on Drug Addiction and Therapy. Aug 3-5, 2015, Orlando FL, U.S.A.
Sharma, S. CB as a novel biomarkers of Zika Virus-Induced Microcephaly. Drug Discovery & Therapy Word Congress. Aug 22-25, 2016. Boston, Mass, U.S.A. (Invited Speaker).
Sharma, S. K., Nayar, U., Maheshwari, M.C, and Gopinath, G. 1986. Ultrastructural studies of P-cell morphology in developing normal and undernourished rat cerebellar cortex. Electrophysiological Correlates. Neurology India. 34: 323-327.
Sharma, S. K., Nayar, U., Maheshwari, M.C. and Singh, B. 1987. Effect of undernutrition on developing rat cerebellum: Some Electrophysiological and Neuromorphological Correlates. J. Neurol. Sciences. 78: 261-272,
Sharma, S., Choga, J., Gupta, V., Doghor, P., Chauhan, A., Kalala, F., Foor, A., Wright, C., Renteria, J., Theberge, K., Mathur, S. 2016. CB as a novel biomarker of nutritional stress in Alzheimer’s Disease. Functional Foods in Health and Disease 6(6), 344-378.
Sharma, S., Ebadi, M. 2014. CB as a Universal Biomarker of Cell Injury. Biomarkers and Genomic Medicine. 6, 89-98.
Sharma, S., Nepal, B., Moon, C., Chabenne, A., Khogali, A., Ojo, C., Hong, E., Gaudet, R., Sayed-Ahmed, A., Jacob, A., Murtuja, A., Firlit, M., 2014. Psychology of Craving. Open Journal of Medical Psychology, 3, 120-125.
Sharma, S., Ebadi, M.

2014

. Significance of metallothioneins in aging brain. Neurochem. Int. 65, 40-48.
Sharma, S.K., Selvamurthy, W. and Dakshinamurti, K. 1993. Effect of environmental neurotoxins in the developing brain. Biometeorology. 2, 447-455.
Sushil Sharma, S., Gawande, S., Jagtap, A., Aboulela, R, Salman. Z. 2015. Fetal Alcohol Syndrome: Prevention, Diagnosis and Treatment. Nova Science Publishers. New Yorks, U.S.A. pp. 39-94.

Chapter 1

Buske, C., Gerlai, R. 2011. Early embryonic Ethanol exposure impairs shoaling and the dopaminergic and serotoninergic systems in adult zebrafish. Neurotoxicol Teratol. 33(6), 698–707.
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Sharma, S. 2017. Zika Virus Disease (Prevention and Cure). Nova Science Publishers, New York, U.S.A.
Sharma, S. Charnoly Body as Novel Biomarker of Drug Addiction. 4th International Congress & exhibition on Drug Addiction and Therapy. Aug 3-5, 2015, Orlando FL, U.S.A.
Sharma, S., Choga, J., Gupta, V., Doghor, P., Chauhan, A., Kalala, F., Foor, A., Wright, C., Renteria, J., Theberge, K., Mathur, S. 2016. CB as a novel biomarker of nutritional stress in Alzheimer’s Disease. Functional Foods in Health and Disease 6(6), 344-378.
Sharma, S. 2016. Monoamine Oxidase Inhibitors. Clinical Pharmacology, Benefits, and Potential Health Risks. Nova Science Publishers. New York.
Sushil Sharma, S., Gawande, S., Jagtap, A., Aboulela, R, Salman. Z. 2015. Fetal Alcohol Syndrome: Prevention, Diagnosis and Treatment. Nova Science Publishers. New York, U.S.A. pp. 39-94.
Sharma, S. 2015. Beyond Diet and Depression. (Vol 1) Nova Science Publishers, New York. U.S.A.
Sharma, S. 2015. Beyond Diet and Depression. (Vol. 2) Nova Science Publishers. New York, U.S.A.
Sharma, S. 2015. Alleviating Stress of the Soldier and Civilian. Nova Science Publishers. New York, U.S.A.
Sharma, S. 2014. Nanotheranostics in evidence based personalized medicine. Curr. Drug Targets. 15(10), 915-930.
Sharma, S., Ebadi, M. 2014. The Charnoly Body (CB) as a Universal Biomarker of Cell Injury. Biomarkers and Genomic Medicine. 6, 89-98.
Sharma, S., Nepal, B., Moon, C., Chabenne, A., Khogali, A., Ojo, C., Hong, E., Gaudet, R., Sayed-Ahmed, A., Jacob, A., Murtuja, A., Firlit, M., 2014. Psychology of Craving. Open Journal of Medical Psychology, 3, 120-125.
Sharma, S., Ebadi, M.

2014

. Significance of metallothioneins in aging brain. Neurochem. Int. 65, 40-48.
Sharma S., Rais, A., Sandhu, R., Nel, W., Ebadi, M. 2013. Clinical significance of metallothioneins in cell therapy and nanomedicine.

Int. J. Nanomedicine. 8, 1477-1488.
Sharma and Ebadi (2011) Therapeutic potential of metallothioneins as anti-inflammatory agents in polysubstance abuse. IIOAB Journal. 2, 50-61.
Sharma, S., Ebadi, M. 2008

Sharma, S., Ebadi, M. 2008

. SPECT neuroimaging in translational research of CNS disorders. Neurochem Int. 52(3), 352-362.
Sharma, S.K., Selvamurthy, W. and Dakshinamurti, K. 1993. Effect of environmental neurotoxins in the developing brain. Biometeorology. 2, 447-455.
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Chapter 2

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Klongpanichapak, S., Govitropong, P., Sharma, S., Ebadi, M., 2006. Attenuation of Cocaine and Methamphetamine neurotoxicity by Coenzyme Q10. Neurochemical Research 31, 303-311.
Kooncumchoo, P., Sharma, S., Porter, J., Govitrapong, P., Ebadi, M., 2006. Coenzyme Q10 provides neuroprotection in iron-induced apoptosis in dopaminergic neurons. Journal of Molecular Neuroscience. 28, 125-141.
Lee, R.W., Shenoy, D.B., Sheel, R., 2010. Micellar Nanoparticles: Applications for Topical and Passive Transdermal Drug Delivery. Chapter 2: p 37-58. Handbook of Non-Invasive Drug Delivery Systems. (Non-Invasive and Minimally-Invasive Drug Delivery Systems for Pharmaceutical and Personal Care Products) A volume in Personal Care & Cosmetic Technology.
Li, Z., Lin, Q., Ma, Q., Lu, C., Tzeng, C.M. 2014. Genetic predisposition to Parkinson's disease and cancer. Curr. Cancer Drug Targets. 14(3), 310-321.
Misra, V., Yang, B., Sharma, S., Savitz, S. 2011. Cell Based Therapy for Stroke. In Therapy for Neurological injury. Ed Charles S Cox Jr. Chapter 7, pp 143-162. Humana Press. Springer Science.
Saiz,, J.C., Ángela Vázquez-Calvo, A., Blázquez, A.B., 2016. ZIKV: the Latest Newcomer. Frontiers in Microbiology. 7, 496.
Sangchot, P., Sharma, S.K., Chetsawang, B, Govitropong, P., Ebadi, M., 2002 Deferoxamine attenuates Iron-Induced Oxidative Stress and prevents Mitochondrial aggregation and α-Synuclein Translocation in SK-N-SH cells in Culture. Developmental. Neuroscience. 24, 143-153.
Shabbir, F., Patel, A., Mattison, C., Bose, S., Krishnamohan, R., Sweeney, E., Sandhu, S., Nel, W., Rais, A., Sandhu, R., Ngu, N., Sharma, S. 2013. Effect of diet on serotonergic neurotransmission in depression. Neurochemistry International, 62 (3), 324-329.
Sharma S (2014) Beyond Diet and Depression (Volume-2) Book Nova Science Publishers, New York, U.S.A.
Sharma S (2015) Alleviating Stress of the Soldier & Civilian. Nova Science Publishers, New York. U.S.A.
Sharma S (2015) Monoamine Oxidase Inhibitors: Clinical Pharmacology, Benefits, & Adverse Effects. Nova Science Publishers, New York. U.S.A.
Sharma S and Ebadi M. (2014) Significance of Metallothioneins in Aging Brain. Neurochemistry International. 2014: 65, 40-48.
Sharma S, Gawande S, Jagtap A, Abeulela R, and Salman Z. Fetal Alcohol Syndrome; Prevention, Diagnosis, & Treatment. In Alcohol Abuse: Prevalence, Risk Factors. Nova Science Publishers, New York, U.S.A. p 39-94.
Sharma S, Nepal B, Moon CS, Chabenne A, Khogali A, Ojo C, Hong E, Goudet R, Sayed-Ahmad A, Jacob A, Murtaba M, Firlit M. (2014) Psychology of Craving. Open Jr of Medical Psychology. 3, 120-125.
Sharma S. (2014) Beyond Diet and Depression (Volume-1) Book Nova Sciences Publishers, New York, U.S.A.
Sharma S. (2014) Nanotheranostics in Evidence Based Personalized Medicine. Current Drug Targets. 15: 915-930.
Sharma S. (2016) Personalized Medicine (Beyond PET Biomarkers) Nova Science Publishers. New York. U.S.A.
Sharma S. (2016) Pet Radiopharmaceuticals for Personalized Medicine. Curr Drug Targets. 17, 1894-1907.
Sharma S. (2016) Progress in PET Radiopharmaceuticals (Quality Control & Theranostics). Nova Science Publishers. New York. U.S.A.
Sharma, S., Ebadi, M., 2011. Therapeutic Potential of Metallothioneins as Anti-inflammatory Agents in Polysubstance Abuse. Journal of Institute of Integrative Omics & Applied Biotechnonogy IIOAB Journal 2, 50-61.
Sharma, S., 2015. Monoamine Oxidase Inhibitors: Clinical Pharmacology, Benefits, & Adverse Effects. Nova Science Publishers, New York. U.S.A.
Sharma, S. 2014. Molecular Pharmacology of Environmental Neurotoxins. In Kainic Acid: Neurotoxic Properties, Biological Sources, and Clinical Applications. Nova Science Publishers. New York. P1-47.
Sharma, S. 2016. Progress in PET Radiopharmaceuticals (Quality Control & Theranostics). Nova Science Publishers. New York. U.S.A.
Sharma, S. 2016e. CB as a Novel Biomarker in ZIKV-Induced Microcephaly. Drug Discovery & Therapy World Congress (DDTWC-2016). Hynes Memorial Conventional Center, Boston, Mass, U.S.A. Aug 21-25. (invited Speaker).
Sharma, S. 2017. Zika Virus Disease (Prevention and Cure) Nova Science Publishers, New York. U.S.A.
Sharma, S. CB as a Novel Biomarker in Drug Addiction. 4th International Conference and Exhibition of Addiction Research & Therapy. Aug 3-5, 2015. Orlando, Florida. U.S.A. (Invited Key Note Lecture displayed on the Google).
Sharma, S. Ebadi, M., 2011. Metallothioneins As Early & Sensitive Biomarkers of Redox Signaling in Neurodegenerative Disorders. Journal of Institute of Integrative Omics & Applied Biotechnonogy (IIOAB Journal) 2, 98-106.
Sharma, S. K., 1985. Mossy fiber evoked unit activity in developing normal and undernourished rat Purkinje cells. Presented and Published in the Proceedings of the 13th World Congress of Neurology at Hamburg, Germany. Sep. 1-6, Vol. 232. p 95.
Sharma, S. K., 1988. Nutrition and Brain Development. Published in the Proceedings of the First World Congress of Clinical Nutrition. New Delhi, (India) p 5-8.
Sharma, S. K., Nayar, U., Maheshwari, M.C, and Gopinath, G., 1986. Ultrastructural studies of P-cell morphology in developing normal and undernourished rat cerebellar cortex. Electrophysiological Correlates. Neurology. India. 34, 323-327.
Sharma, S. K., Nayar, U., Maheshwari, M.C. and Singh, B., 1987. Effect of undernutrition on developing rat cerebellum: Some Electrophysiological and Neuromorphological Correlates. Journal of Neurolological Sciences. 78, 261-272.
Sharma, S. K., Nayar, U., Maheshwari, M.C., Singh, B., 1993b. Purkinje Cell evoked unit activity in developing undernourished rats. Journal of Neurolological Sciences 116, 212-219.
Sharma, S., 2013. CB as a sensitive biomarker in Nanomedicine. International Translational Nanomedicine Conference. Boston, July 26-28. (Invited Speaker).
Sharma, S., 2014. Beyond Diet and Depression (Volume-1) Book Nova Sciences Publishers, New York, U.S.A.
Sharma, S., 2014a. Beyond Diet and Depression (Volume-2) Book Nova Science Publishers, New York, U.S.A.
Sharma, S., 2014b. Beyond Diet and Depression (Volume-1) Book Nova Sciences Publishers, New York, U.S.A.
Sharma, S., 2014c. Molecular Pharmacology of Environmental Neurotoxins. In Kainic Acid: Neurotoxic Properties, Biological Sources, and Clinical Applications. Nova Science Publishers. New York. P 1-47.
Sharma, S., 2014d. CB as a Universal Biomarker in Nanomedicine, 2nd International Translational Nanomedicine Conference. Boston, July 25-27 (Invited Speaker).
Sharma, S., 2014e. Mitochondrially-Targeted Nanomedicines. 5th World Gene Conference. Haikou, China Nov 13-15 (Invited Speaker and Chairperson).
Sharma, S., 2014f. CB as a Universal Biomarker in Drug Discovery. 12th International Conference on Drug Discovery. Suzhou, China Nov 18-20 (Invited Speaker & Chair Person).
Sharma, S., 2014g. Nanotheranostics in Evidence Based Personalized Medicine. Current Drug Targets. 15, 915-930.
Sharma, S., 2014h Charnolopharmacotherapy in Multi-Drug Resistant Diseases. 5th International Conference in MediChem. Suzhou, China Nov 18-20 (Invited Speaker).
Sharma, S., 2014i. Charnolopharmacotherapy of Cancer and other Diseases. 5th International Conference, Suzhou, China, Nov 18-20 (Invited Speaker).
Sharma, S., 2015. Alleviating Stress of the Soldier & Civilian. Nova Science Publishers, New York. U.S.A.
Sharma, S., 2015a. Alleviating Stress of the Soldier & Civilian. Nova Science Publishers, New York. U.S.A.
Sharma, S., 2015b. Monoamine Oxidase Inhibitors: Clinical Pharmacology, Benefits, & Adverse Effects. Nova Science Publishers, New York. U.S.A.
Sharma, S., 2015c. CB as a Universal Biomarker in Drug Addiction. 3rd International Drug Addiction Conference. Orlando, Florida. USA. Aug, 2-5.
Sharma, S., 2016. Personalized Medicine (Beyond PET Biomarkers) Nova Science Publishers. New York. U.S.A.
Sharma, S., 2016a. Personalized Medicine (Beyond PET Biomarkers). Nova Science Publishers, New York. U.S.A.
Sharma, S., 2016b. Progress in PET Radiopharmaceuticals. Nova Science Publishers, New York. U.S.A.
Sharma, S., 2016c. Disease-Specific CB formation in Neurodegenerative & Other Diseases. Drug Discovery & Therapy World Congress. Aug 22-25. Hynes International Convention Center. Boston Mass. U.S.A. (Invited Speaker).
Sharma, S., 2016d. CB as novel biomarker of Nutritional Stress in Alzheimer’s Disease. 20 th International Coference of Functional Foods in Health & Disease. Josheph P. Martin Memorial Convention Center, Harvard Medical School, Boston, Mass, U.S.A. Sep 22-23 (Invited Speaker).
Sharma, S., Bing, Y., Brenneman, M., Xiaopei, Xi., Aronowski, J., Grotta, J., Savitz, S., 2010. Bone Marrow Mononuclear Cells Protect Neurons and Modulate Microglia in Cell Culture Models of Ischemic Stroke. Journal of Neuroscience Research. 88, 2869-2876.
Sharma, S., Carlson, E., Ebadi, M., 2003. The neuroprotective actions of selegiline in inhibiting 1-methyl, 4-phenyl, pyridinium ion (MPP+)-induced apoptosis in dopaminergic neurons. Journal of Neurocytology. 32, 329–343.
Sharma, S., Choga J., Gupta, V., Doghor, P, Chauhan, A., Kalala, F., Foor, A., Wright, C., Rentereria, J., Theberge, K.E., Mathur, S. 2016. CB as a novel biomarker of nutritional stress in Alzheimer’s Disease. Functional Foods in Health and Disease 6, 344-377
Sharma, S., Choga, J., Doghor, P. et al. 2016a CB as a novel biomarker of Nutritional Stress in Alzheimer’s Disease. 20th International Conference on Functional Foods in Health & Disease. Joseph P. Martin International Convention Center, Harvard Medical School, Boston. Mass., U.S.A. Sep 22-23.
Sharma, S., Choga, J., Gupta, V., 2016b. CB as a novel biomarker of nutritional stress in Alzheimer’s Disease. Functional Foods in Health and Disease. 6, 344-378.
Sharma, S., Choga, J., Gupta, V., et al., 2016. CB as a Novel Biomarker of Nutritional Stress in Alzheimer’s Disease. Functional Foods in Health & Disease. 6, 344-377.
Sharma, S., Ebadi, M., 2014. In-Vivo Molecular Imaging in Parkinson’s Disease. In Parkinson’s Disease, Eds M. Ebadi and R. Pfieffer. CRC Press, Boca Rotan FL. U.S.A
Sharma, S., Ebadi, M., 2003. Metallothionein attenuates 3-morpholinosydnonimone (SIN-1)-induced oxidative and nitrative stress in dopaminergic neurons. Antioxidant and Redox Signaling 5, 251–264.
Sharma, S., Ebadi, M., 2008a. Coenzyme Q10 Augments Brain Regional 18F-DOPA and 2-18F-Fluoro, 2-Deoxy, D-Glucose Uptake in Metallothionein Over-expressing Weaver Mouse. Proceedings of the World Congress of Molecular Imaging (WMIC 2008). Sep 10-13, 2008.
Sharma, S., Ebadi, M., 2008b. Therapeutic Potential of Metallothioneins in Parkinson’s Disease. In New Research on Parkinson’s Disease. Eds: Timothy F. Hahn & Julian Werner, Nova Science Publishers, New York, pp 1-28.
Sharma, S., Ebadi, M., 2011a. Metallothioneins As Early & Sensitive Biomarkers of Redox Signaling in Neurodegenerative Disorders. Journal of Institute of Integrative Omics & Applied Biotechnonogy (IIOAB Journal) 2, 98-106.
Sharma, S., Ebadi, M., 2011b. Therapeutic Potential of Metallothioneins as Anti-inflammatory Agents in Polysubstance Abuse. Journal of Institute of Integrative Omics & Applied Biotechnonogy IIOAB Journal 2, 50-61.
Sharma, S., Ebadi, M., 2013 In-Vivo Molecular Imaging in Parkinson’s Disease. In Parkinson’s Disease. Eds. RF. Pfeiffer, ZK Wszolek, M. Ebadi. IInd Edition, Chapter 58, CRC Press Taylor & Francis Group. Boca Rotan, FL, USA. pp. 787-802.
Sharma, S., Ebadi, M., 2013. Antioxidant Targeting in Neurodegenerative Disorders. Ed. I. Laher, Springer Verlag. Germany. Chapter 85, p 1-30.
Sharma, S., Ebadi, M., 2013. In-Vivo Molecular Imaging in Parkinson’s Disease. In Parkinson’s Disease. Eds. RF. Pfeiffer, ZK Wszolek, M. Ebadi. IInd Edition, Chapter 58, CRC Press Taylor & Francis Group. Boca Rotan, FL, USA. pp. 787-802.
Sharma, S., Ebadi, M., 2014. The Charnoly Body as a Universal Biomarker of Cell Injury. Biomarkers and Genomic Medicine 6, 89–98.
Sharma, S., Ebadi, M., 2014a. Antioxidants as potential therapeutics in neurodegeneration. I. Laher (Ed.), System Biology of Free Radicals and Antioxidants, Springer Verlag, Heidelberg, Germany, Chapter 85, pp. 1–30.
Sharma, S., Ebadi, M., 2014b. CB as a Universal Biomarker of Cell Injury. Biomarkers and Genomic Medicine. 6, 89-98.
Sharma, S., Ebadi, M., 2014c. Significance of Metallothioneins in Aging Brain. Neurochemistry International. 65, 40-48.
Sharma, S., Gawande, S., Jagtap, A., Abeulela, R., and Salman, Z., 2014a. Fetal Alcohol Syndrome; Prevention, Diagnosis, & Treatment. In Alcohol Abuse: Prevalence, Risk Factors. Nova Science Publishers, New York, U.S.A.
Sharma, S., Kheradpezhou, M., Shavali, S., EI Refaey, H., Eken, J., Hagen, C., Ebadi, M., 2004. Neuroprotective Actions of Coenzyme Q10 in Parkinson’s Disease. Methods in Enzymology. 382, 488-509.
Sharma, S., Moon, C.S., Khogali, A., Haidous, A., Chabenne, A., Ojo, C., Jelebinkov, M., Kurdi, Y., Ebadi, M., 2013. Biomarkers of Parkinson’s Disease (Recent Update). Neurochemistry International. 63, 201-229.
Sharma, S., Moon, C.S., Khogali, A., Haidous, A., Chabenne, A., Ojo, C., Jelebinkov, M., Kurdi, Y., Ebadi, M. 2013. Biomarkers of Parkinson’s Disease (Recent Update). Neurochemistry International. 63, 201-229.
Sharma, S., Nepal, B., Moon, C.S., Chabenne, A., Khogali, A., Ojo, C., Hong, E., Goudet, R., Sayed-Ahmad, A., Jacob, A., Murtaba, M., Firlit, M., 2014b. Psychology of Craving. Open Jr of Medical Psychology. 3, 120-125.
Sharma, S., Rais, A., Sandhu, R., Nel, W., Ebadi, M. 2013. Clinical significance of metallothioneins in cell therapy and nanomedicine. International Journal of Nanomedicine. 8, 1477–1488. (Video Movie is available on the Journal’s Web Site).
Sharma, S., Rais, A., Sandhu, R., Nel, W., Ebadi, M., 2013. Clinical significance of metallothioneins in cell therapy and nanomedicine. International Journal of Nanomedicine. 8, 1477–1488.
Sharma, S., Refaey, H. El., Ebadi, M., 2006. Complex-1 activity and 18F-DOPA uptake in genetically engineered mouse model of Parkinson’s disease and the neuroprotective role of coenzyme Q10. Brain Research Bulletin. 70, 22-32.
Sharma, S., Yang, B., Xi, X., Grotta, J., Aronowski, J., Savitz, S., 2011. IL-10 Directly Protects Cortical Neurons by Activating PI-3 Kinase and STAT-3 Pathways. Brain Research. 1373, 189-194.
Sharma, S., Yang, B., Xi, X., Grotta, J., Aronowski, J., Savitz, S., 2011. IL-10 Directly Protects Cortical Neurons by Activating PI-3 Kinase and STAT-3 Pathways. Brain Res 1373, 189-194.
Sharma, S.,2014. Beyond Diet and Depression (Volume-2) Book Nova Science Publishers, New York, U.S.A.
Sharma, S.K., Selvamurthy, W. and Dakshinamurti, K., 1993a. Effect of environmental neurotoxins in the developing brain. Biometeorology. 2, 447-455.
Wang, E., 2009. MicroRNA Regulation and its Biological Significance in PM and Aging. Current Genomics 10, 143.
Wang, J.J., Zeng, Z.W., Xiao, R.Z., et al. 2011. Recent advances of chitosan nanoparticles as drug carriers. International Journal of Nanomedicine. 6, 765-774.
Yang, B., Strong, R., Sharma, S., Brenneman, M., Malikarjunarao, K., Xi, X., Grotta, J.C., Aronowski, J., Savitz, S.I., 2010. Therapeutic Time Window and Dose-Response of Autologous Bone Marrow Mononuclear Cells for Ischemic Stroke. J. Neurosci. Res. 89, 833-839.
Zhang., S., Lei, C., Liu, P., 2015. Association between variant amyloid deposits and motor deficits in FAD-associated presenilin-1 mutations: A systematic review. Neuroscience & Biobehavioral Reviews. 56, 180-192.

Chapter 13

Guantes, R., Rastrojo, A., Neves, R., Lima, A., Aguado, B., Iborra, F.J.. 2015. Global variability in gene expression and alternative splicing is modulated by mitochondrial content. Genome Res. May; 25(5), 633-644.
Guantes, R., Díaz-Colunga, J., Iborra, F.J. 2016. Mitochondria and the non-genetic origins of cell-to-cell variability: More is different. Bioessays. 38(1), 64-76.

Chapter 14

Chu, J., Tong, M., de la Monte, S.M. Chronic Ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons. Acta Neuropathol. 2007 Jun;113(6), 659-673.
de La Monte, S.M., Wands, J.R.2001. Mitochondrial DNA damage and impaired mitochondrial function contribute to apoptosis of insulin-stimulated Ethanol-exposed neuronal cells. Alcohol Clin. Exp. Res. 25, 898-906.
Heaton, M.B., Paiva, M., Siler-Marsiglio, K. 2011. Ethanol influences on Bax translocation, mitochondrial membrane potential, and reactive oxygen species generation are modulated by vitamin E and brain-derived neurotrophic factor. Alcohol Clin. Exp. Res. 35(6), 1122-1133.
Henderson, G.I., Devi, B.G., Perez, A., Schenker, S. 1995. In utero Ethanol exposure elicits oxidative stress in the rat fetus. Alcohol Clin Exp Res. 19(3), 714-20.

Hewitt, A.J., Walker, K.R., Kobus, S.M., Poklewska-Koziell, M., Reynolds, J.N., Brien, J.F. 2010. Differential effects of chronic Ethanol exposure on cytochrome P450 2E1 and the hypothalamic-pituitary-adrenal axis in the maternal-fetal unit of the guinea pig. Neurotoxicol Teratol. 32(2),164-170.
Marin-Garcia, J., Ananthakrishnan, R., Goldenthal, M.J.1996. Mitochondrial dysfunction after fetal Alcohol exposure. Alcohol Clin Exp Res. 20(6),1029-1032.
Naseer, M.I., Ullah, I., Narasimhan, M.L., Lee, H.Y., Bressan, R.A., Yoon, G.H., Yun, D.J., Kim, M.O. 2014. Neuroprotective effect of osmotin against Ethanol-induced apoptotic neurodegeneration in the developing rat brain. Cell Death Dis. 5, e1150.
Ullah, I, Ullah, N, Naseer, M.I, Lee, H.Y., Kim, M.O. 2012. Neuroprotection with metformin and thymoquinone against Ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons. BMC Neurosci. 13, 11.
Xu, Y. J, Liu, P., Li, Y. 2005. [Effect of Alcohol on brain mitochondria development of mouse embryos]. Wei Sheng Yan Jiu. 34(1), 61-63.

Chapter 15

Bing, R.J. 1982. Effect of Alcohol on the heart and cardiac metabolism. Fed. Proc. 41(8), 2443-2446.
de la Monte SM, Wands JR. 2010. Role of central nervous system insulin resistance in fetal Alcohol spectrum disorders. J. Popul. Ther. Clin. Pharmacol. 17(3), e390-404.
de La Monte, S.M., Wands, J.R. 2001. Mitochondrial DNA damage and impaired mitochondrial function contribute to apoptosis of insulin-stimulated Ethanol-exposed neuronal cells. Alcohol Clin. Exp. Res. 25(6), 898-906.
Elpeleg, O., Mandel, H., Saada, A. 2002. Depletion of the other genome-mitochondrial DNA depletion syndromes in humans. J. Mol. Med (Berl). 80(7), 389-396.
Kennedy, J.M., Kelley, S. W., Meehan, J.M. 1993. Ventricular mitochondrial gene expression during development and following embryonic Ethanol exposure. J. Mol. Cell Cardiol. 25(2), 117-1131.
Langevin, F., Crossan, G.P., Rosado, I.V., Arends, M.J., Patel, K.J. 2011. Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice. Nature. 475(7354), 53-58.
Ledig, M., Misslin, R., Kopp, P., Vogel, E., Tholey, G., Mandel, P. 1990. Alcohol exposure before pregnancy: biochemical and behavioral effects on the offspring of rats. Pharmacol. Biochem. Behav. 36(2), 279-285.
Vaudry, D., Cécile Rousselle, C., Basille, M. 2002. Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against Ethanol-induced apoptotic cell death. Proc Natl Acad Sci U S A. 99(9), 6398–6403.

Chapter 16

Balaraman, S., Lunde, E.R, Sawant O, Cudd TA, Washburn SE, Miranda RC. 2014. Maternal and neonatal plasma microRNA biomarkers for FAE in an ovine model. Alcohol Clin. Exp. Res. 38(5), 1390-400.
Balaraman, S., Schafer, J.J., Tseng, A.M., Wertelecki, W., Yevtushok, L., Zymak-Zakutnya, N., Chambers, C.D., Miranda, R.C. 2016. Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following PAE. PLoS One. 11(11), e0165081.
Balaraman, S., Tingling, J.D., Tsai, P.C., Miranda, R.C. 2013. Dysregulation of microRNA expression and function contributes to the etiology of fetal Alcohol spectrum disorders. Alcohol Res. 35(1), 18-24.
Bing RJ. 1982. Effect of Alcohol on the heart and cardiac metabolism. Fed. Proc. 41(8), 2443-2446.
Chen, X., Liu, J., Feng, W.K., Wu, X., Chen, S.Y. 2015. MiR-125b protects against Ethanol-induced apoptosis in neural crest cells and mouse embryos by targeting Bak 1 and PUMA. Exp. Neurol. 271, 104-111.
Chu, J., Tong, M., de la Monte, S.M. 2007. Chronic Ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons. Acta Neuropathol. 113(6), 659-673.
Crabb, D.W., Matsumoto, M., Chang, D., You, M. 2004. Overview of the role of Alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of Alcohol-related pathology. Proc. Nutr. Soc. 63(1), 49-63.
de la Monte SM, Wands JR. 2010. Role of central nervous system insulin resistance in fetal Alcohol spectrum disorders. J. Popul. Ther. Clin. Pharmacol. 17(3), e390-404.
de La Monte, S.M., Wands, J.R. 2001. Mitochondrial DNA damage and impaired mitochondrial function contribute to apoptosis of insulin-stimulated Ethanol-exposed neuronal cells. Alcohol Clin. Exp. Res. 25(6), 898-906.
Devi, B.G., Henderson, G.I., Frosto, T.A., Schenker, S. 1993. Effect of Ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione. Hepatology. 18(3), 648-659.
Elpeleg, O., Mandel, H., Saada, A. 2002. Depletion of the other genome-mitochondrial DNA depletion syndromes in humans. J. Mol. Med (Berl). 80(7), 389-396.
Heaton MB, Paiva M, Siler-Marsiglio K. 2011. Ethanol influences on Bax translocation, mitochondrial membrane potential, and reactive oxygen species generation are modulated by vitamin E and brain-derived neurotrophic factor. Alcohol Clin. Exp. Res. 35(6), 1122-1133.
Henderson, G.I., Devi, B.G., Perez, A., Schenker, S. 1995. In utero Ethanol exposure elicits oxidative stress in the rat fetus. Alcohol Clin. Exp. Res. 19(3), 714-720.
Hewitt, A.J., Walker, K.R., Kobus, S.M., Poklewska-Koziell, M., Reynolds, J.N., Brien, J.F. 2010. Differential effects of chronic Ethanol exposure on cytochrome P450 2E1 and the hypothalamic-pituitary-adrenal axis in the maternal-fetal unit of the guinea pig. Neurotoxicol Teratol. 32(2),164-170.
Ignacio, C., Mooney, S.M., Middleton, F.A. 2014. Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment. Front. Pediatr. 2, 103.
Joenje, H. 2011. Metabolism: Alcohol, DNA and disease. Nature. 475(7354), 45-46.
Kennedy, J.M., Kelley, S. W., Meehan, J.M. 1993. Ventricular mitochondrial gene expression during development and following embryonic Ethanol exposure. J. Mol. Cell Cardiol. 25(2), 117-1131.
Kitsiou-Tzeli, S., Tzetis, M. 2016. Maternal epigenetics and fetal and neonatal growth. Curr. Opin. Endocrinol. Diabetes Obes. (in press).
Kleiber, M.L., Diehl, E.J., Laufer, B.I., Mantha, K., Chokroborty-Hoque, A., Alberry, B., Singh, S.M. 2014. Long-term genomic and epigenomic dysregulation as a consequence of PAE: a model for fetal Alcohol spectrum disorders. Front Genet. 5, 161.

Kleiber, M.L., Laufer, B.I., Stringer, R.L., Singh, S.M. 2014. Third trimester-equivalent Ethanol exposure is characterized by an acute cellular stress response and an ontogenetic disruption of genes critical for synaptic establishment and function in mice. Dev. Neurosci. 36(6), 499-519.
Langevin, F., Crossan, G.P., Rosado, I.V., Arends, M.J., Patel, K.J. 2011. Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice. Nature. 475(7354), 53-58.
Laufer, B.I., Mantha, K., Kleiber, M.L., Diehl, E.J., Addison, S.M., Singh, S.M. 2013. Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of FAE in mice. Dis. Model Mech. 6(4), 977-992.
Ledig, M., Misslin, R., Kopp, P., Vogel, E., Tholey, G., Mandel, P. 1990. Alcohol exposure before pregnancy: biochemical and behavioral effects on the offspring of rats. Pharmacol. Biochem. Behav. 36(2), 279-285.
Mantha, K., Laufer, B. I., Singh, S.M. 2014. Molecular changes during neurodevelopment following second-trimester binge Ethanol exposure in a mouse model of fetal Alcohol spectrum disorder: from immediate effects to long-term adaptation. Dev Neurosci. 36(1), 29-43.
Marin-Garcia, J., Ananthakrishnan, R., Goldenthal, M. J. 1996. Mitochondrial dysfunction after FAE. Alcohol Clin. Exp. Res. 20(6),1029-1032.
Miranda, R.C. 2012. MicroRNAs and Fetal Brain Development: Implications for Ethanol Teratology during the Second Trimester Period of Neurogenesis. Front. Genet. 3, 77.
Naseer MI, Ullah I, Narasimhan ML, Lee HY, Bressan RA, Yoon GH, Yun DJ, Kim MO. 2014. Neuroprotective effect of osmotin against Ethanol-induced apoptotic neurodegeneration in the developing rat brain. Cell Death Dis. 5, e1150.
Pulakat, L., Aroor, A.R., Gul, R., Sowers, J.R. 2012. Cardiac insulin resistance and microRNA modulators. Exp. Diabetes Res. 2012, 654904.
Qi, Y., Zhang, M., Li, H., Frank, J.A., Dai, L., Liu, H., Chen, G. 2014. MicroRNA-29b regulates Ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR cascade. J. Biol. Chem. 289(14), 10201-10210.
Resendiz M, Mason S, Lo CL, Zhou FC. 2014. Epigenetic regulation of the neural transcriptome and Alcohol interference during development. Front. Genet. 5, 285.
Soares, A.R., Pereira, P.M., Ferreira, V., Reverendo, M., Simões, J., Bezerra, A.R., Moura, G.R., Santos, M.A. 2012. Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos. Toxicol Sci. 127(1), 18-28.
Stringer, R.L., Laufer, B.I., Kleiber, M.L., Singh, S.M. 2013. Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal Alcohol spectrum disorders. Clin. Epigenetics. 5(1), 14.
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Chapter 21

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Chapter 22

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Chapter 23

Bonthius, D.J., Luong, T., Bonthius, N.E., Hostager, B.S., Karacay, B. 2009. Nitric oxide utilizes NF-kappaB to signal its neuroprotective effect against Alcohol toxicity. Neuropharmacology. 56(3),716-731.
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Lindsley, T.A., Shah, S.N., Ruggiero, E.A. 2011. Ethanol alters BDNF-induced Rho GTPase activation in axonal growth cones. Alcohol Clin. Exp. Res. 35(7), 1321-1330.
Lindsley, T.A., Shah, S.N., Ruggiero, E.A. 2011. Ethanol alters BDNF-induced Rho GTPase activation in axonal growth cones. Alcohol Clin. Exp. Res. 35(7), 1321-1330.
Luo, J., Miller, M.W. 1997. Differential sensitivity of human neuroblastoma cell lines to Ethanol: correlations with their proliferative responses to mitogenic growth factors and expression of growth factor receptors. Alcohol Clin Exp Res. 21(7), 1186-1194.
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Mitchell, J.J., Paiva, M., Moore, D.B., Walker, D.W., Heaton, M.B. 1998. A comparative study of Ethanol, hypoglycemia, hypoxia and neurotrophic factor interactions with fetal rat hippocampal neurons: a multi-factor in vitro model developmental Ethanol effects. Brain Res Dev Brain Res. 105(2), 241-250.

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This book provides basic and applied knowledge about FASD, its basic molecular mechanism of occurrence during prezygotic and postzygotic phase due to Ethanol-induced diversified charnolopathies. Basic knowledge of emerging charnolopharmacotherapeutics is provided for the safe and effective clinical management of FASD. The book will be valuable source of new knowledge for doctors, patients, medical students, teachers, researchers, and basic biomedical scientists.

The book will be highly useful for general public interested in learning more about FASD without any misconception and/or misunderstanding for its prevention and/or treatment to prevent chronic diseases, early morbidity, and mortality.

Neonatologists, Pediatricians, Neurologist, and Neuropsychiatrists will find this book interesting for the effective clinical management of FASD victims. The book will be of immediate interest to FASD parents and FASD victims to alleviate their sufferings.

Physicians interested in prescribing and learning more about FASD and their molecular and pharmacological mechanism(s) of neuroprotection will find this book high beneficial. They will be highly benefited from its informative and basic and clinically-interesting contents.

In general, the book will be a valuable source of knowledge for the basic researcher, clinically useful for the physician, and therapeutically-beneficial for FASD patients and their families.

In addition to physicians, the book can be a valuable for Masters and Ph. D students interested in conducting further research on FASD for the effective clinical management of various associated neurological and psychiatric disorders like ADHD in these patients.

Particularly, MD doctors, students, and professors will find this book interesting and informative to enhance their basic existing knowledge about FASD and its prevention and/or treatment for a better quality of life.

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