Aerobic exercise upregulates the BDNF-Serotonin systems and improves the cognitive function in rats.

Aerobic exercise (AE) benefits brain health and behavior. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known to mediate and shape cognitive processes. Both systems share some actions: BDNF is involved in the maturation and function of 5-HT neurons. In turn, 5-HT is involved in neuroplasticity phenomena mediated by BDNF and stimulated by exercise. The aim of this work was to study the long-term effects of AE on BDNF- 5-HT systems and cognitive function in rats at different ages. A lifelong moderate-intensity aerobic training program was designed, in which aerobically exercised (E) and sedentary control (C) rats were studied at middle (8 months) and old age (18 months) by means of biochemical, immunohistochemical and behavioral assays. The levels and expression of BDNF, 5-HT, serotonin transporter (SERT) and 5-HT1A receptor were determined in selected brain areas involved in memory and learning. Immunopositive cells to neuronal nuclear protein (NeuN) in the hippocampus CA1 area were also quantified. The cognitive function was evaluated by the object recognition test (ORT). Results indicate that AE enhanced spatial and non-spatial memory systems, modulated by age. This outcome temporarily correlated with a significant upregulation of cortical, hippocampal and striatal BDNF levels in parallel with an increase in the number of hippocampal CA1-mature neurons. AE also increased brain and raphe 5-HT levels, as well as the expression of SERT and 5-HT1A receptor in the cortex and hippocampus. Old AE rats showed a highly conserved response, indicating a remarkable protective effect of exercise on both systems. In summary, lifelong AE positively affects BDNF-5-HT systems, improves cognitive function and protects the brain against the deleterious effects of sedentary life and aging.

Direct effects of ethanol on neuronal differentiation: An in vitro analysis of viability and morphology.

The deleterious effects of ethanol (EtOH) on the brain have been widely described, but its effects on the neuronal cytoskeleton during differentiation have not yet been firmly established. In this context, our aim was to investigate the direct effect of EtOH on cortical neurons during the period of differentiation. Primary cultures of cortical neurons obtained from 1-day-old rats were exposed to EtOH after 7days of culture, and viability and morphology were analyzed at structural and ultrastructural levels after 24-h EtOH exposure. EtOH caused a significant reduction of 73±7% in the viability of cultured cortical neurons, by preferentially inducing apoptotic cellular death. This effect was accompanied by an increase in caspase 3 and 9 expression. Furthermore, EtOH induced a reduction in total dendrite length and in the number of dendrites per cell. Ultrastructural studies showed that EtOH increased the number of lipidic vacuoles, lysosomes and multilamellar vesicles and induced a dilated endoplasmatic reticulum lumen and a disorganized Golgi apparatus with a ring-shape appearance. Microtubules showed a disorganized distribution. Apposition between pre- and postsynaptic membranes without a defined synaptic cleft and a delay in presynaptic vesicle organization were also observed. Synaptophysin and PSD95 expression, proteins pre- and postsynaptically located, were reduced in EtOH-exposed cultures. Overall, our study shows that EtOH induces neuronal apoptosis and changes in the cytoskeleton and membrane proteins related with the establishment of mature synapses. These direct effects of EtOH on neurons may partially explain its effects on brain development.

Differential and irreversible CNS ontogenic reduction in maximal MK-801 binding site number in the NMDA receptor after acute hypoxic hypoxia.

CNS exposure to hypoxia impairs excitatory and inhibitory neurotransmission. Our aim was to determine variations induced by normobaric acute hypoxic hypoxia (8% O(2) for 60 min) on the NMDA receptor complex, as well as their potential reversibility after normoxic recovery. To this end, [3H]MK-801 binding assays to a synaptic membrane fraction isolated from chick optic lobes were performed. Previous studies throughout development had disclosed a characteristic age-dependent pattern. Results at embryonic day (ED) 12 and 18 indicated two distinct MK-801 binding sites. Hypoxic treatment failed to alter either the high affinity site dissociation constant (K(d)) or its maximal binding capacity (B(max)), whereas the low affinity site B(max) was significantly decreased (50% and 30% at ED12 and 18, respectively), without alteration in its K(d) values. Hypoxic embryos restored for 48 h at ED12 to normoxic conditions displayed unchanged MK-801 binding reduction, unlike those treated likewise at ED18 whose values fully recovered control levels. To conclude, hypoxic treatment reduces low affinity MK-801 B(max) in the NMDA receptor which proves irreversible up to ED12. Such early neuronal vulnerability may be due to post-transcriptional changes, to endocytosis followed by receptor degradation, or alternatively to cell death.