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M
etallothianeins (MT) and their four isoforms play a predominant role in coping up with the oxidative damage in the neurons
and glial cells in the retina, pineal gland and especially in the hippocampus. MTs help sequestering zinc in the synaptic
vesicles and maintaining redox potentials. It is documented that there is a varying concentration in zinc levels in several CNS
disorders including chronic alcoholism. Along with genes regulating MTs , there are 639 genes affected due to chronic alcohol
consumption like glucocorticoid receptor and the related gene
FK506
Binding protein 5 (FKBP5), UDP Glycosyltranferase 8
(UGT8), urea transporter (SLC1A1) and interleukin 1 receptor type 1 (IL1R1). NF- kB signaling pathway leads to deleterious
effects on hippocampus as the alcohol affects the genes modulating the cortisol pathway regulation and inflammation. There is
also a study showing changes in the genes related to hypothalamic neurons made up of proopiomelanocortin (
POMC
) derived
peptides leading to stress, metabolic and immune dysfunctions in people with family history of chronic alcoholism. In
POMC
neurons, the histone modifying proteins and DNA methyl transferase levels are altered and CPG di-nucleotides are increased
in the proximal part of
POMC
promoter region. The epigenetic modification in
POMC
gene transmits through generation
via male germ line as it was found that hyper methylation of the
POMC
gene was detected in sperm of the exposed offspring.
A significant rise in
c-fos
gene is observed in offspring of chronically alcohol treated rats which may be the reason for the
development of alcoholic motivation in the off springs of chronically alcohol treated animals
Biography
Akshaya Kambhatla, MD completed her graduated from Andhra Medical College in 2011. She was honored with Gold Medal for outstanding performance in
Pathology during 2008 from N.T.R. University of Health Sciences, India. She served as Secretary of National Service Scheme (NSS), a volunteer of organization
wing in her medical school from 2008-2010. She completed her USMLE exams and she is doing her rotations in various hospital setups to get US Clinical
experience
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