Caffeine prevents age-associated recognition memory decline and changes brain-derived neurotrophic factor and tirosine kinase receptor (TrkB) content in mice.

The beneficial effects of caffeine on cognition are controversial in humans, whereas its benefit in rodents had been well characterized. However, most studies were performed with acute administration of caffeine and the tasks used to evaluate cognition had aversive components. Here, we evaluated adulthood administration of caffeine up to old age on recognition memory in mice using the object recognition task (ORT) and on brain-derived neurotrophic factor (BNDF) and tyrosine kinase receptor (TrkB) immunocontent in the hippocampus. Adult mice (6 months old) received either drinking water or caffeine (1 mg/mL) during 12 months. At 18 months of age both groups were tested for ORT. Our results showed that aged mice exhibited lower performance in the recognition memory compared with adults (6 months old). Furthermore, caffeine-treated mice showed similar performance to adult mice in the ORT and an improvement compared with their age-matched control mice. Caffeine also counteracted the age-related increase in BDNF and TrkB immunocontent. Our results corroborate with other studies and reinforce that caffeine consumed in adulthood may prevent recognition memory decline with aging. This preventive effect may involve a decrease in the hippocampal BDNF and TrkB immunocontent.

Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice.

BACKGROUND AND PURPOSE: Caffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by adenosine A2 A receptor, but not A1 receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice. EXPERIMENTAL APPROACH: We determined whether A2 A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A2 A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. KEY RESULTS: Scopolamine (1.0 mg·kg(-1) , i.p.) impaired short-term memory performance in all three tests and this scopolamine-induced amnesia was prevented by the A2 A receptor antagonist (SCH 58261, 0.1-1.0 mg·kg(-1) , i.p.) and by the A1 receptor antagonist (DPCPX, 0.2-5.0 mg·kg(-1) , i.p.), except in the modified Y-maze where only SCH58261 was effective. Both antagonists were devoid of effects on memory or locomotion in naïve rats. Notably, the activation of A2 A receptors with CGS 21680 (0.1-0.5 mg·kg(-1) , i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg(-1) , i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. CONCLUSIONS AND IMPLICATIONS: These results show that A2 A receptors are necessary and sufficient to trigger memory impairment and further suggest that A1 receptors might also be selectively engaged to control the cholinergic-driven memory impairment.

The impact of the frequency of moderate exercise on memory and brain-derived neurotrophic factor signaling in young adult and middle-aged rats.

The participation of the brain-derived neurotrophic factor (BDNF) in the benefits of physical exercise on cognitive functions has been widely investigated. Different from voluntary exercise, the effects of treadmill running on memory and BDNF are still controversial. Importantly, the impact of the frequency of physical exercise on memory remains still unknown. In this study, young adult and middle-aged rats were submitted to 8 weeks of treadmill running at moderate intensity and divided into 4 groups of frequency: 0, 1, 3 and 7 days/week. Aversive and recognition memory were assessed as well as the immunocontent of proBDNF, BDNF and tyrosine kinase receptor type B (TrkB) in the hippocampus. Frequencies did not modify memory in young adult animals. The frequency of 1 day/week increased proBDNF and BDNF. All frequencies decreased TrkB immunocontent. Middle-aged animals presented memory impairment along with increased BDNF and downregulation of TrkB receptor. The frequency of 1day/week reversed age-related recognition memory impairment, but worsened the performance in the inhibitory avoidance task. The other frequencies rescued aversive memory, but not recognition memory. None of frequencies altered the age-related increase in the BDNF. Seven days/week decreased proBDNF and there was a trend toward increase in the TrkB by the frequency of 1 day/week. These results support that the frequency and intensity of exercise have a profound impact on cognitive functions mainly in elderly. Thus, the effects of physical exercise on behavior and brain functions should take into account the frequency and intensity.