Neuroscience
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Neuroendocrine secretion often requires prolonged voltage-gated Ca(2+) entry; however, the ability of Ca(2+) from intracellular stores, such as endoplasmic reticulum or mitochondria, to elicit secretion is less clear. We examined this using the bag cell neurons, which trigger ovulation in Aplysia by releasing egg-laying hormone (ELH) peptide. Secretion from cultured bag cell neurons was observed as an increase in plasma membrane capacitance following Ca(2+) influx evoked by a 5-Hz, 1-min train of depolarizing steps under voltage-clamp. ⋯ Employing GTP-γ-S to interfere with endocytosis delayed recovery (presumed membrane retrieval) of the capacitance change following FCCP, but not the train. Finally, secretion was correlated with reproductive behavior, in that neurons isolated from animals engaged in egg-laying presented a greater train-induced capacitance elevation vs quiescent animals. The bag cell neuron capacitance increase is consistent with peptide secretion requiring high Ca(2+), either from influx or stores, and may reflect the all-or-none nature of reproduction.
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Although extensive evidence demonstrates that repeated administration of amphetamine (AMPH) induces behavioral and neurochemical sensitization, the influence of the developmental timing of AMPH administration is unknown. This is an important issue to address because it could help clarify the influence of early drug exposure on neuronal plasticity and the involvement of dopaminergic sensitization in the etiopathology of neuropsychiatric disorders. ⋯ We found that peri-pubertal treatment with AMPH induces long-lasting changes in the expression of bdnf and of activity-regulated genes in the hippocampus and in the prefrontal/frontal cortex, and leads to alterations of their short-term modulation in response to a subsequent acute AMPH challenge. These data suggest that AMPH exposure in peri-puberty may negatively affect the maturation of brain structures, such as the prefrontal cortex, which facilitate the development of dopamine sensitization and may contribute to dopamine-dependent behavioral dysfunctions and molecular alterations in adulthood.
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Blood-brain barrier (BBB) dysfunction is a feature of many neurodegenerative disorders. The mechanisms and interactions between astrocytes, extracellular matrix and vascular endothelial cells in regulating the mature BBB are poorly understood. We have previously shown that transitory glial fibrillary acidic protein (GFAP)-astrocyte loss, induced by the systemic administration of 3-chloropropanediol, leads to reversible disruption of tight junction complexes and BBB integrity to a range of markers. ⋯ In addition, the extracellular matrix, as visualized by laminin and fibronectin, underwent extensive reversible remodeling and perivascular CD169 macrophages become abundant throughout the lesioned inferior colliculus. At a time that GFAP-astrocytes repopulated the lesion area and tight junction proteins were returned to paracellular domains, the extracellular matrix and leukocyte profiles normalized and resembled profiles seen in control tissue. This study supports the hypothesis that a combination of paracellular adherens junctional proteins, remodeled basement membrane and the presence of perivascular leukocytes provide a temporary barrier to limit the extravasation of macromolecules and potentially neurotoxic substances into the brain parenchyma until tight junction proteins are restored to paracellular domains.
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Hydrogen sulfide (H2S) is a gasotransmitter endogenously generated from the metabolism of L-cysteine by action of two main enzymes called cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). This gas has been involved in the pain processing and insulin resistance produced during diabetes development. However, there is no evidence about its participation in the peripheral neuropathy induced by this metabolic disorder. ⋯ Paradoxically, H2S levels were decreased in nerve sciatic, dorsal root ganglion and spinal cord, but not paw nor blood plasma, during diabetes-associated peripheral neuropathy development. Collectively, results suggest that H2S synthesized by CBS and CSE participate in formalin-induced nociception in diabetic and non-diabetic rats, as well as; in tactile allodynia in streptozotocin-injected rats. In addition, data seems to indicate that diabetic rats are more sensible to H2S-induced hyperalgesia than normoglycemic rats.
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The zebra finch song system provides an excellent model to study the mechanisms underlying the development of sex difference in brain structure and function. Only male zebra finches sing and the brain nuclei controlling song learning and production are considerably larger than in females. Sexual differentiation may in part be regulated by estrogen, but other molecules including neurotrophic factors likely also affect masculinization. ⋯ The number of immunopositive cells increased in males and decreased in females as they matured, in a pattern generally consistent with a role for BDNF in sensorimotor integration of song learning. In addition, in HVC (but not RA) the ratio of mature BDNF compared to its precursor proBDNF was greater in adult males than those at post-hatching day 25, indicating a region-specific shift in the relative availability of the two forms. Collectively, the data suggest that changes in BDNF protein expression across development may be associated with song system maturation, particularly during the sensorimotor integration of masculine vocalizations.