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

Biomed Pharmacother. 2017 Mar:87:721-740. doi: 10.1016/j.biopha.2016.12.020. Epub 2017 Jan 14.

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.

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.

Keywords: Alcohol; BDNF; CREB-P; Curcumin; Neurodegeneration.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Curcumin / pharmacology*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Ethanol / adverse effects
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Interleukin-1beta / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotection / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Interleukin-1beta
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Superoxide Dismutase
  • Glutathione
  • Curcumin
  • Glutathione Disulfide