Caffeine neuroprotective effects on 6-OHDA-lesioned rats are mediated by several factors, including pro-inflammatory cytokines and histone deacetylase inhibitions
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2014-05-01
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Machado-Filho, Joao Ananias
Correia, Alyne Oliveira
Aires Montenegro, Anyssa Brilhante
Pereira Nobre, Maria Elizabeth
Cerqueira, Gilberto Santos
Tavares Neves, Kelly Rose
Naffah-Mazzacoratti, Maria da Graca [UNIFESP]
Cavalheiro, Esper Abrao [UNIFESP]
Castro Brito, Gerly Anne de
Barros Viana, Glauce Socorro de
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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 20 mg/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-alpha, IL-1 beta 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-alpha and IL-1 beta. All these effects points out to a neuroprotective effect of caffeine and its potential benefit in the prevention and treatment of PD. (C) 2014 Elsevier B.V. All rights reserved.
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Behavioural Brain Research. Amsterdam: Elsevier B.V., v. 264, p. 116-125, 2014.