Caffeine neuroprotective effects on 6-OHDA-lesioned rats are mediated by several factors, including pro-inflammatory cytokines and histone deacetylase inhibitions

Behav Brain Res. 2014 May 1:264:116-25. doi: 10.1016/j.bbr.2014.01.051. Epub 2014 Feb 10.

Abstract

Several lines of evidences have shown the inversion association between coffee consumption and Parkinson's disease (PD) development. Caffeine is a methylxanthine known as a non-selective inhibitor of A2A and A1 adenosine receptors in the brain and shown to be a neuroprotective drug. The objectives were to study caffeine effects in a unilateral 6-OHDA model of PD in rats. Male rats were divided into the following groups: sham-operated (SO), striatal 6-OHDA-lesioned and 6-OHDA-lesioned and treated for 2 weeks with caffeine (10 and 20mg/kg, p.o.). Then, animals were subjected to behavioral (open field and apomorphine-induced rotations), neurochemical (striatal determinations of DA and DOPAC), histological (cresyl violet staining) and immunohistochemical (TH, TNF-α, IL-1β and HDAC) evaluations. The results showed that while the 6-OHDA group presented a decreased locomotor activity and a high number of apomorphine-induced rotations, these behaviors were partially blocked by caffeine. Caffeine itself increased DA contents and reversed the decrease in striatal DA observed in the 6-OHDA-lesioned group. Furthermore, it improved the hippocampal neuronal viability and significantly increased TH immunoreactivity in the striatum of the 6-OHDA-lesioned group. In addition, caffeine treatment also decreased the number of immunopositive cells for HDAC and pro-inflammatory cytokines TNF-α and IL-1β. All these effects points out to a neuroprotective effect of caffeine and its potential benefit in the prevention and treatment of PD.

Keywords: 6-OHDA model; Behavior; Caffeine; Neuroprotection; Parkinson's disease; Pro-inflammatory cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Adrenergic Agents / toxicity
  • Animals
  • Apomorphine / pharmacology
  • Brain / metabolism
  • Caffeine / pharmacology*
  • Caffeine / therapeutic use
  • Cytokines / metabolism*
  • Dopamine / metabolism
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Histone Deacetylases / metabolism*
  • Male
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidopamine / toxicity
  • Parkinson Disease / drug therapy
  • Parkinson Disease / etiology
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Rats
  • Rats, Wistar
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Adrenergic Agents
  • Cytokines
  • Dopamine Agonists
  • Neuroprotective Agents
  • 3,4-Dihydroxyphenylacetic Acid
  • Caffeine
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Histone Deacetylases
  • Apomorphine
  • Dopamine