[Abstract Title]. - Society for Neuroscience

FCT Grant PTDC/SAU-NEU/81064/2006
Fundo Fundação Oriente/Johnson & Johnson
FCT Grant PTDC/SAU-NEU/74318/2006
Title: Chronic caffeine consumption prevents memory deficits in animal models of diabetic
neuropathy, chronic unpredictable stress or juvenile convulsions
Authors: *R. A. CUNHA, G. P. COGNATO, M. P. KASTER, J. M. N. DUARTE, P. M.
CANAS;
Ctr. for NeuroSci of Coimbra, Inst. Biochem, Fac Med, Univ. Coimbra, Coimbra, Portugal
Abstract: Caffeine (an adenosine receptor antagonist at non-toxic doses) is the most widely
consumed psychoactive drug. Its chronic consumption prevents memory deficits upon aging or
Alzheimer‟s disease, an effect mimicked by adenosine A2A receptor antagonists in animal
models. We now tested if caffeine also affords protection in other diseases also leading to
memory dysfunction, such as stress, childhood convulsions or diabetes. A protocol of chronic
unpredictable stress for 3 weeks in c57Bl6 mice increased immobility in the forced swim test and
decreased both spontaneous alternation and time spent in a novel arm in a Y-maze test; chronic
caffeine consumption (1 g/L in the drinking water starting 4 weeks before beginning and
throughout the stress paradigm) prevented this stress-induced memory deficit, as well as the
stress-induced astrogliosis and loss of immunoreactivity of presynaptic markers (SNAP-25,
syntaxin) in the hippocampus. The induction of a convulsive episode in post-natal day 7 (PN7)
Wistar rats by kainate ip injection lead to a reduction of the number of entrances in a novel arm
of a Y-maze apparatus, determined to evaluate response to novelty (2 minutes inter-trial interval)
and spatial recognition memory (2 hours inter-trial interval) at PN90 (but not PN30 or PN60);
caffeine consumption (1 g/L in the drinking water starting at P21) abrogated this
developmentally-related memory dysfunction at PN90 caused by a convulsive period in infancy.
Since diabetes is associated with an increased risk of cognitive dysfunction mainly in older
adults, we studied the effect of caffeine treatment (1 g/L caffeine in drinking water during 4
months) in a mouse model of type 2 diabetes associated with obesity (NONcNZO10/Ltj, 12
months-old). These diabetic mice displayed a reduced spontaneous alternation in the Y-maze test
and an increased astrogliosis and reduced density of synaptic proteins (SNAP25 and
synaptophysin) in the hippocampus; caffeine consumption reduced body weight and glycaemia
of diabetic mice, abrogated memory deficits and attenuated both astrogliosis and synaptotoxicity.
These results support the notion that the chronic consumption of caffeine, possibly acting
through A2A receptor blockade, confers a robust protection against memory deficits in different
noxious brain conditions.
Disclosures: R.A. Cunha, FCT, B. Research Grant (principal investigator, collaborator or
consultant and pending grants as well as grants already received); Fundação Oriente, B. Research
Grant (principal investigator, collaborator or consultant and pending grants as well as grants
already received); G.P. Cognato, CAPES, B. Research Grant (principal investigator,
collaborator or consultant and pending grants as well as grants already received); FCT, B.
Research Grant (principal investigator, collaborator or consultant and pending grants as well as