title: Caffeine neuroprotective effects on 6-OHDA-lesioned rats are mediated by several factors, including pro-inflammatory cytokines and histone deacetylase inhibitions.
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.
authors: Faculty of Medicine Estácio of Juazeiro do Norte, Brazil.
authors: João Ananias
authors: JA
authors: Machado-Filho
authors: Faculty of Medicine Estácio of Juazeiro do Norte, Brazil.
authors: Alyne Oliveira
authors: AO
authors: Correia
authors: Faculty of Medicine Estácio of Juazeiro do Norte, Brazil.
authors: Anyssa Brilhante Aires
authors: AB
authors: Montenegro
authors: Faculty of Medicine Estácio of Juazeiro do Norte, Brazil.
authors: Maria Elizabeth Pereira
authors: ME
authors: Nobre
authors: Faculty of Medicine of the Federal University of Ceará, Brazil.
authors: Gilberto Santos
authors: GS
authors: Cerqueira
authors: Faculty of Medicine of the Federal University of Ceará, Brazil.
authors: Kelly Rose Tavares
authors: KR
authors: Neves
authors: Department of Experimental Neurology of the Federal University of São Paulo, Brazil.
authors: Maria da Graça
authors: Mda G
authors: Naffah-Mazzacoratti
authors: Department of Experimental Neurology of the Federal University of São Paulo, Brazil.
authors: Esper Abrão
authors: EA
authors: Cavalheiro
authors: Faculty of Medicine of the Federal University of Ceará, Brazil.
authors: Gerly Anne
authors: GA
authors: de Castro Brito
authors: Faculty of Medicine Estácio of Juazeiro do Norte, Brazil; Faculty of Medicine of the Federal University of Ceará, Brazil. Electronic address: gbviana@live.com.
authors: Glauce Socorro
authors: GS
authors: de Barros Viana
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D016207:Cytokines; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D002110:Caffeine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D006655:Histone Deacetylases; D001058:Apomorphine; D004298:Dopamine
keywords: 6-OHDA model; Behavior; Caffeine; Neuroprotection; Parkinson's disease; Pro-inflammatory cytokine