Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.
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.


RESULT
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.


CONCLUSION
Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway.
['Motaghinejad|Majid|M|', 'Motevalian|Manijeh|M|', 'Fatima|Sulail|S|', 'Hashemi|Hajar|H|', 'Gholami|Mina|M|']
D000818:Animals D019208:Brain-Derived Neurotrophic Factor D003474:Curcumin D017362:Cyclic AMP Response Element-Binding Protein D000431:Ethanol D005978:Glutathione D019803:Glutathione Disulfide D006624:Hippocampus D053583:Interleukin-1beta D015227:Lipid Peroxidation D008297:Male D008928:Mitochondria D019636:Neurodegenerative Diseases D009474:Neurons D000066829:Neuroprotection D018696:Neuroprotective Agents D018384:Oxidative Stress D010766:Phosphorylation D051381:Rats D017208:Rats, Wistar D015398:Signal Transduction D013482:Superoxide Dismutase D014409:Tumor Necrosis Factor-alpha
Curcumin Neurodegeneration Alcohol BDNF CREB-P