title: All trans retinoic acid (ATRA) mediated modulation of N-methyl D-aspartate receptor (NMDAR) and Kruppel like factor 11 (KLF11) expressions in the mitigation of ethanol induced alterations in the brain.
abstract: BACKGROUND
  Damaging effects that chronic ethanol exposure causes to the brain and the neurons are well documented. Ethanol and its toxic metabolites increase the oxidative stress in brain. Chronic exposure to ethanol leads to upregulation of N-methyl D-aspartate receptors (NMDAR) and also activates Kruppel like factor 11 (KLF11) mediated death cascade and thereby neurodegeneration.
  
  
  OBJECTIVE
  Ethanol depletes vitamin A stores. But supplementation of vitamin A exacerbates ethanol induced toxicity since alcohol and its metabolites are competitive inhibitors of the enzymes involved in the metabolism of vitamin A. Hence, in this study we investigated the impact of co-administration of ethanol and all trans retinoic acid (ATRA), active metabolite of vitamin A, on ethanol induced alterations to the brain.
  
  
  METHODS
  Male Sprague Dawley rats, adolescent, were grouped as follows and maintained for 90 days. I - Control, II - Ethanol (4 g/kg b.w.), III - ATRA (100 µg/kg b.w.), IV - Ethanol (4 g/kg b.w.), +ATRA (100 µg/kg b.w.). Oxidative stress and the mRNA expression of various receptors for the neurotransmitter involved in glutamergic, serotonergic and gabaergic pathways were studied in the brain homogenate.
  
  
  RESULTS
  Ethanol treatment was shown to decrease brain weight and it was increased on ATRA treatment. Increase in oxidative stress due to ethanol treatment was also brought down on ATRA administration. Ethanol induced upregulation of NMDAR and KLF11 was also downregulated on ATRA supplementation. The alterations in the levels of neurotransmitters and the expression of their receptors due to ethanol treatment also were ameliorated on ATRA supplementation.
  
  
  CONCLUSIONS
  Our results show that ATRA supplementation mitigates the ethanol induced alterations in the brain by reducing oxidative stress in the brain with concurrent suppression of NMDAR and KLF11 expression leading to enhanced catabolism of neurotransmitters.
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram-695 581, Kerala, India.
authors.forename: Saritha S
authors.initials: SS
authors.lastname: Nair
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram-695 581, Kerala, India.
authors.forename: P
authors.initials: P
authors.lastname: Prathibha
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram-695 581, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Syam Das
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram-695 581, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Kavitha
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram-695 581, Kerala, India. Electronic address: indiramadambath@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Indira
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017459:Receptors, Amino Acid / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism
chemical_list: C569356:KLF11 protein, rat; D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D015534:Trans-Activators; C031959:aspartic acid receptor; D014801:Vitamin A; D000431:Ethanol; D014212:Tretinoin
keywords: All trans retinoic acid; Monoamine oxidases; NMDAR; Neurodegeneration; Neurotransmitters; Oxidative stress