Feng C. Zhou, Ph.D.
Professor of Anatomy & Cell Biology
Ph.D. Mount Sinai, University of New York (1983)
Neurobiology of Neurodegenerative and Neurodevelopmental Disorder.
In my opinion, the nervous system not only responds but also reacts to environmental changes and insult. The neural system has intricate molding ability after injury - making and reshaping dendritic spines, sprouting and regenerating axons, reprogramming receptor reception and subtypes, altering signal transduction, activating neurotrophic response, and mobilizing neural stem cells - collectively called neuroadaptation. Neurodaptation may underlie the mechanisms of substance abuse, altered states of mind, and the repair of neurodegenerative/neurodevelopmental disorders.
Neural Stem Cells, Neural Transplantation and Neurodegenerative Disease.
Using a neurotrophic factor, epidermal and fibroblast growth factor, we have isolated the stem cells in the fetal brain and adult spinal cord. Departing from the method of B. Reynold's laboratory in Canada, we have developed a new method for the preservation of stem cells (Chiang, Silani and Zhou, 1996). We have found that injury in the brain and spinal cord increases neural stem cell production. These stem cells can survive in the culture for years and continue to proliferate, and differentiate into various types of neurons, such as serotonin, dopamine, spinal cord, and dorsal root gangalial neurons. We are interested in understanding what contributes to keeping and departing-from stem-cell-ship (Zhou et al., 2001, Restorative Neurology Neurosci, 18:95-104, 2001) and the application of neural stem cells for degenerative diseases such as spinal cord injury, parkinsonism, and hypo-serotonin depression. We are also investigating how to guide transplanted cells to send projecting axons to targeted brain regions using BDNF, excitatory amino acid, and extracellular matrix (Zhou and Chiang, and Wang, J. Neuroscience, 1996; Zhou and Chiang, Cell Transplantation, 1995). We are pursuing this bridging transplant technique for repairing brain damage resulting n open circuitry.
Alcohol abuse and Neurodevelopmental disorder.
Repeated exposure to selective neuronal reactive substances can induce neuroadaptation. Repeated alcohol drinking may alter neurochemical as well as neuroanatomical components of the brain circuitry. A study of a genetically bred line of rats which drink excess alcohol revealed that a lower content of monoamine exists in several brain regions of the Alcohol-Preferring (P) as compared with the Non-Preferring (NP) rats (McBride et al., 2000). Our studies have shown that P rats have fewer serotonin (5-HT) neuron in raphe and less 5-HT and dopamine innervation in the reward circuitry of the brain (Zhou et al., 1994, 1995). Lines of evidence suggest that the dopamine and serotonin systems may be involved in predetermination of alcohol-seeking behavior, as well as anxiety and sensory-motor behavior. Increasing serotonin in the synaptic level, reduces the alcohol-seeking tendency in P rats (Zhou et al., 1998). Currently, we are investigating how chronic alcohol exposure turns the brain into an "addictive" state. We believe the altered brain undergoes neuroadaptation at the synaptic level. Using two-photon microscopy, we are monitoring presynaptic glutamate and dopamine terminals, and postsynaptic NMDA, AMPA, mGluR, and D1/D2 receptors on dendritic spines in the reward circuitry.
Alcohol exposure during development places the nervous system in double jeopardy-it damages the nerve cells and disturbs the neural program. Fetal alcohol syndrome featuring microencephaly, neural underdevelopment, facial dysmorphology, and psychosocial disorder is a leading non-genetic cause of mental retardation in the western world. We have found fetal alcohol disturbs the neural tube particularly in the midline which compromises the timely formation of raphe and renders fewer serotonin neurons in the brain (Zhou et al., 2001, 2003, Sari et al., 2001). We are currently and in future studies the following questions: Serotonin has been considered a signal for differentiation - How will fewer serotonin neurons affect the developing cortices and sensory system which depending on 5-HT for fine tuning? Serotonin in the mature brain mediates mental states and cardiopulmonary function and its dysfunction cause affective disorders - How will fewer serotonin neurons affect brain function and related behaviors? Together, how will the nervous system adapt itself when it is disturbed in the early stage?
Selected Peer-Reviewed Publications
- Chen Y, Öztürk NC, Zhou FC. "DNA Methylation Program in Developing Hippocampus and its Alteration by Alcohol." PLOS1. In press.
- Solzak J, Liang Y, Zhou FC, Roper R. Commonality in Down and Fetal Alcohol Syndromes, Birth Defects Research (A): Clinical and Molecular Teratology. In press.
- Resendiz M, Chen Y, Öztürk NC, Zhou FC. Epigenetic Medicine and Fetal Alcohol Spectrum Disorders. Epigenomics. 2013 (5) 73-86 (doi: 10.2217/epi.12.80).
- Zhou, FC. DNA Methylation Program During Development. Frontiers in Biology, 2012 (7) 485-494. ISSN: 1674-7984 (Print) 1674-7992 (Online). DOI: 10.1007/s11515-012-9246-1.
- Zhou, F. C. and R. L. Bell (2012). "Editorial: Pharmacotherapies for the treatment of alcohol abuse and dependence." Recent Pat CNS Drug Discov7(2) 91-92.
- Mason S, Anthony B, Lai X, Ringham H, Wang M, Witzmann FA, You JS, Zhou FC. Ethanol Exposure Alters Protein Expression in a Mouse Model of Fetal Alcohol Syndrome. International J Proteomics. Int J Proteomics 2012: 867141.
- Beversdorf DQ, Nordgren RE Bonab A A , Fischman A J , Weise S B, Dougherty DD, Felopulos G J, Zhou FC , Bauman ML. 5-HT2 receptor distribution shown by [18F] setoperone PET in high-functioning autistic adults. Neuropsychiatry Clin Neurosci 2012 (24)191-197.
- Zhou FC, Balaraman Y, Teng M, Liu Y, Singh RP, Nephew KP (2011a) Alcohol Alters DNA Methylation Patterns and Inhibits Neural Stem Cell Differentiation. Alcohol Clin Exp Res, in press. NIHMSID: NIHMS252373
- Zhou FC, Zhao. Q., Liu Y, Goodlett CR, Liang T, McClintick J, Edenberg HJ, Li L (2011b) Alteration of Gene Expression by Alcohol Exposure At Early Neurulation. BMC genomics, 12:124. PMCID:PMC3056799
- Zhou FC, Chen, Y., Love, A. (2011c) Cellular DNA Methylation Program during Neurulation and its Alteration by Alcohol Exposure. Birth Defects Res A Clin Mol Teratol. 2011 91(8)703-15. doi: 10.1002/bdra.20820; PMID:21630420.
- Singh RP. Cheng YH, Nelson P, and Zhou FC, Tenacious Multipotency of Adult Dorsal Root Ganglial Stem Cells. Cell Transplant. 2009;18(1):55-68
- Singh RP, Shiue K, Schomberg D, Zhou FC. Cellular Epigenetic Modifications of Neural Stem Cell Differentiation. Cell Transplant. 2009; 18(10): 1197–1211. PMCID: PMC2812652
- Liu Y, Balaraman Y, Wang G, Nephew K, and Zhou FC. Alcohol Exposure Alters DNA Methylation Profiles in Mouse Embryos at Early Neurulation. Epigenetics, 2009(4)1-12. PMCID: PMC2805036
- Wang G, Wang X, Li L, Edenberg HJ, Zhou FC, and Liu Y. Identification of transcription factor and microRNA binding sites from array-derived gene expression data. BMC Genomics 2008, 9(Suppl 1):S1-19. PMCID: PMC2386061.
- Zhou, FC, Anthony, B, Dunn, K., Deng, P, Xu, Z, and Lidquist, W.B. Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens, Brain Res. 2007;1134(1):148-61.
- Chiang, YH, Lin, SZ, Zhou, FC. Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in Parkinsonian rats. Cell Transplant. 2006;15(6):475-82.
- Chandler LJ, Carpenter-Hyland E, Hendricson AW, Maldve RE, Morrisett RA, Zhou FC, Sari Y, Bell R, Szumlinski KK. Structural and functional modifications in glutamateric synapses following prolonged ethanol exposure. Alcohol Clin Exp Res.30(2006):368-76.
- Zhou, FC, Sahr, R. N., Sari, Y., Behbahani, K. Glutamate and dopamine synaptic terminals in extended amygdala after 14-week chronic alcohol drinking in inbred alcohol-preferring rats. Alcohol, 39(2006):39-49.
- Zhou FC, Sari, Y, Powrozek T, and Spong CY. A neuroprotective peptide antagonizes fetal alcohol exposure compromised brain growth. J. Mole. Neurosci, 24(2004)189-199.
- Zhou, FC., Duguid, JR., Edenberg, HJ., McClintick, J, Young, P, and Nelson, P. (2001) DNA microarray analysis of Differential gene expression of 6-year-old rat neural Striatal Progenitor cells during early differentiation. Restorative Neurology Neurosci, 18:95-104
- Zhou, FC, Kelley, M. R., and Chiang, Y.H., and Young P. (2000) Three to four-year old non-passaged EGF-responsive neural progenitor cells: proliferation, apoptosis and DNA-repair. Exp Neurol. 164:200-208.
- Zhou, FC and Bledsoe, S. (1996) Methamphetamine causes rapid varicosis, perforation and definitive degeneration of serotonin fibers: an immunocytochemical study of serotonin transporter, Neuroscience-Net, V.1, Article 10009, Oct. 28,1996, http://www.neuroscience.com/.
- Zhou, FC, Chiang, YH, and Wang, Y. (1996) Constructing a new nigrostriatal pathway in the parkinsonian model with bridged neural transplantation in substantia nigra. J. Neurosci. 16, 6965-6974
- Chen Y, Öztürk NC, Zhou FC. "DNA Methylation Program in Developing Hippocampus and its Alteration by Alcohol." PLOS1. 2013. DOI: 10.1371/journal.pone.0060503. PubMed PMID: 23544149; PubMed Central PMCID: PMC3609790.
- Solzak J, Liang Y, Zhou FC, Roper R. Commonality in Down and Fetal Alcohol Syndromes, Birth Defects Research (A): Clinical and Molecular Teratology. (2013), Birth defect Res; A Clin Mol Teratol, 97: 187-9. PubMed Central PMCID: PMC4096968.
- Shen L, Ai H, Liang Y, Ren X, Anthony CB, Goodlett CR, Ward R, Zhou FC. Effect of Prenatal Alcohol Exposure on Bony Craniofacial Development: A Mouse MicroCT Study, Alcohol, Alcohol 2013;47(5):405-415. doi: 10.1016/j.alcohol.2013.04.005. PMID: 23809873. PMCID: PMC3732041.
- Hu JG, Wang XF, Deng LX, Liu NK, Gao X, Chen JH, Zhou FC, Xu XM. Cotransplantation of glial restricted precursor cells and Schwann cells promotes functional recovery after spinal cord injury. Cell Transplant. 2013;22(12):2219-36. doi: 10.3727/096368912X661373. Epub 2013 Jan 2. PubMed PMID: 23295060.
- Shim JW, Dodge TR, Hammond MA, Wallace JM, Zhou FC, and Yokota H. Physical Weight Loading Induces Expression of Tryptophan Hydroxylase 2 in the Brain Stem. PLOS ONE, 2014, 9, e85095. PMID: 24416346; PubMed Central PMCID: PMC3885668.
- Chen Y, Damayanti N, Irudayaraj J, Dunn K, Zhou FC. Diversity of two forms of DNA methylation in the brain, Frontiers in Genetics. 5(2014)1-13, doi: 10.3389/fgene.2014.00046, PubMed Central PMCID 3948076.
- Lossie, A. C. Muir, W. M. Lo, C. L. Timm, F. Liu, Y. Gray, W. Zhou, F. C. Implications of genomic signatures in the differential vulnerability to fetal alcohol exposure in C57BL/6 and DBA/2 mice. Front Genetics, 5(2014)173-187. doi: 10.3389/fgene.2014.00173. PMCID4052096.
- Resendiz M, Mason S, Lo C, and Zhou FC. Epigenetic Regulation of the Neural Transcriptome and Alcohol Interference During Development. Front Genetics, 2014 Aug 26;5:285. PubMed Central PMCID:PMC4144008.
- Zhou FC, Dissecting FASD Through the Global Transcriptome. 2015 Alcohol Clin Exp Res, 39:408-412. PMCID: PMC4348334.
- Mason S, Zhou FC. Editorial: Genetics and epigenetics of fetal alcohol spectrum disorders. Front Genet 2015; 6: 146. PMCID: PMC4399412.
Book/ Special Issue Editorial
- “Stem Cells”, Ed. FC Zhou, Current Neurovascular Research. Volume 1, Number 3, July 2004.
- “Pharmacotherapies for the treatment of alcohol abuse and dependence." Ed. FC Zhou and R Bell. Recent Patents on CNS Drug Discovery. volume 7, number 2, 2012. Bentham Science Publishers.
- ”Genetics and Epigenetic of Fetal Alcohol Syndrome” in Frontiers of Genetics, Ed. FC Zhou & S Mason, Front Genetetics: Epigenomics and Epigenetics. 2015. http://journal.frontiersin.org/researchtopic/1941/genetics-and-epigenetics-of-fetal-alcohol-spectrum-disorders#comments.