Neuroscience
-
Regular physical exercise has been described as a good strategy for prevention or reduction of musculoskeletal pain. The Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) has been investigated as a promising target for the control of inflammatory pain. Therefore, the aim of this study was to evaluate whether activation of PPARγ receptors is involved in the reduction of acute muscle pain by chronic exercise and, in this case, whether this process is modulated by inflammatory cytokines. ⋯ The results showed that swimming physical training prevented the onset of acute mechanical muscle hyperalgesia and the increase in muscle levels of Cytokine-induced neutrophil chemoattractant 1 (CINC-1) induced by carrageenan into gastrocnemius muscle. In addition, local pre-treatment with the selective PPARγ receptors antagonist GW9662 reversed the mechanical muscle hypoalgesia and the modulation of CINC-1 levels induced by swimming physical training. These data suggest that swimming physical training prevented the onset of acute mechanical muscle hyperalgesia by a mechanism dependent of PPARγ receptors, which seems to contribute to this process by modulation of the pro-inflammatory cytokine CINC-1, and highlight the potential of PPARγ receptors as a target to control musculoskeletal pain and to potentiate the reduction of musculoskeletal pain induced by exercise.
-
Neurotransmitter release is mediated by ceramide, which is generated by sphingomyelin hydrolysis. In the present study, we examined whether synaptosomal-associated protein 25 (SNAP-25) is involved in ceramide production and exocytosis. Neutral sphingomyelinase 2 (nSMase2) was partially purified from bovine brain and we found that SNAP-25 was enriched in the nSMase2-containing fractions. ⋯ Moreover, transfection of SNAP-25 siRNA inhibited dopamine release, whereas addition of C6-ceramide to the siRNA-treated cells moderately reversed this inhibition. Additionally, nSMase2 inhibition reduced dopamine release. Collectively, our results indicate that SNAP-25 interacts with nSMase2 during ceramide production, which mediates exocytosis and neurotransmitter release.
-
Females are more prone to cognitive decline, stroke and neurodegenerative disease, possibly due to more marked reductions in cerebral blood flow and cerebrovascular reactivity to CO2 (CVRCO2HYPER) in later life. To what extent regular exercise confers selective neuroprotection in females remains unestablished. To examine this, 73 adults were prospectively assigned to 1 of 4 groups based on sex (male, ♂ vs. female, ♀) and physical activity status (trained, ≥150 min of moderate-vigorous intensity aerobic exercise/week; n = 18♂ vs. 18♀ vs. untrained, no formal exercise; n = 18♂ vs. 19♀). ⋯ Despite having a lower VO2MAX, females were characterized by selective elevations in MCAv, CVRCO2HYPER and lower CVRi (P < 0.05), but the training responses were similar across sexes. Linear relationships were observed between VO2MAX and CVRCO2HYPER (pooled untrained and trained data; ♂ r = 0.70, ♀ r = 0.51; both P < 0.05) with a consistent elevation in the latter equivalent to ∼1.50%.mmHg-1 compared to males across the spectrum of cardiorespiratory fitness. These findings indicate that despite having comparatively lower levels of cardiorespiratory fitness, the neuroprotective benefits of regular exercise translate into females and may help combat cerebrovascular disease in later life.
-
Not all the people that consume drugs of abuse develop addiction. In this sense, just a percentage of rats express locomotor sensitization after repeated psychostimulant exposure. Neurochemical evidence has shown that locomotor sensitization is associated with changes in dorsolateral striatum (DLS) activity. ⋯ A decrease in MSNs baseline Lv accompanies the expression of AMPH locomotor sensitization. Moreover, a decrease in Lv after an acute AMPH 1.0 mg/kg injection was only observed in saline and sensitized rats. Our results show individual differences in DLS basal DA levels and firing pattern after repeated AMPH administration, suggesting that an hyperfunction of nigrostriatal pathway, accompanied by a decrease in DLS MSNs firing irregularity underlies the expression of AMPH locomotor sensitization.