Caffeine Consumption Prevents Memory Impairment, Neuronal Damage, and Adenosine A_2A Receptors Upregulation in the Hippocampus of a Rat Model of Sporadic Dementia

Article type: Research Article

Authors: Espinosa, Janaína^a | Rocha, Andreia^a | Nunes, Fernanda^a | Costa, Marcelo S.^a | Schein, Vanessa^a | Kazlauckas, Vanessa^a | Kalinine, Eduardo^a | Souza, Diogo O.^a | Cunha, Rodrigo A.^{b; c} | Porciúncula, Lisiane O.^{a; *}

Affiliations: [a] Laboratory of Studies on the Purinergic System, Federal University of Rio Grande do Sul, Health and Basic Sciences Institute, Department of Biochemistry, Porto Alegre/RS, Brazil | [b] CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal | [c] FMUC-Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Correspondence: [*] Correspondence to: Lisiane O. Porciúncula, Federal University of Rio Grande do Sul, Health and Basic Sciences Institute, Department of Biochemistry, Porto Alegre/RS 90035 003, Brazil. E-mail: [email protected].

Abstract: Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-β-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.

Keywords: Adenosine receptors, Alzheimer's disease, caffeine, memory, streptozotocin

DOI: 10.3233/JAD-111982

Journal: Journal of Alzheimer's Disease, vol. 34, no. 2, pp. 509-518, 2013