Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions.

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.