title: Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.
abstract: BACKGROUND
  Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear.
  
  
  METHODS
  Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting.
  
  
  RESULTS
  Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters.
  
  
  CONCLUSIONS
  Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway.
authors.affiliation: Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Motaghinejad
authors.affiliation: Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: motevalian.m@iums.ac.ir.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Motevalian
authors.affiliation: Department of Physiology, Tehran University of Medical Sciences, International Campus, Tehran, Iran.
authors.forename: Sulail
authors.initials: S
authors.lastname: Fatima
authors.affiliation: Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hajar
authors.initials: H
authors.lastname: Hashemi
authors.affiliation: Department of Medical Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Gholami
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D013482:Superoxide Dismutase; D005978:Glutathione; D003474:Curcumin; D019803:Glutathione Disulfide
keywords: Alcohol; BDNF; CREB-P; Curcumin; Neurodegeneration