Neuroscience
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Adolescence is a critical period of brain maturation characterized by the reorganization of interacting neural networks. In particular the prefrontal cortex (PFC), a region involved in executive function, undergoes synaptic and neuronal pruning during this time in both humans and rats. Our laboratory has previously shown that rats lose neurons in the medial prefrontal cortex (mPFC) and there is an increase in white matter under the frontal cortex between adolescence and adulthood. ⋯ These results suggest that in females, pubertal hormones may exert temporally specific changes in PFC anatomy. As expected, both males and females gained white matter under the PFC throughout adolescence, though these gains in females were diminished after day 35, but not in males. The differences in cell loss in males and females may lead to differential vulnerability to external influences and dysfunctions of the PFC that manifest in adolescence.
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Probenecid has been used for decades to treat gout, and recent studies have revealed it is also a specific inhibitor of the pannexin-1 channel. It has been reported that the pannexin-1 channel is involved in ischemic injury. Here, we investigated the neuroprotective effect and the possible mechanisms of action of probenecid in global cerebral ischemia/reperfusion (I/R) injury in rats. ⋯ The release of cathepsin B and overexpression of calpain-1 after reperfusion were inhibited, while the upregulation of Hsp70 was strengthened by probenecid pre-treatment. Furthermore, the activation and proliferation of microglia and astrocytes after I/R injury were suppressed by continuous given for 7days, but only partly by a single dose at 6h of reperfusion. Thus, our data indicate that probenecid protects against transient global cerebral I/R injury probably by inhibiting calpain-cathepsin pathway and the inflammatory reaction.
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Brain ischemia/reperfusion injury results in death of vulnerable neurons and extensive brain damage. It is well known that mitochondrial release of cytochrome c (cyto c) is a hallmark of neuronal death, however the molecular events underlying this release are largely unknown. ⋯ We found that ischemia/reperfusion induces cyto c release and cell death that corresponds to multiple changes in OPA1, including: (i) translocation of the mitochondrial fusion protein OPA1 from the mitochondria to the cytosol, (ii) increase in the short isoform of OPA1, suggestive of proteolytic processing, (iii) breakdown of OPA1 oligomers in the mitochondria, and (iv) increased mitochondrial fission. Thus, we present novel evidence of a connection between release of cyto c from mitochondria and disruption of the mitochondrial fusion.
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Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. ⋯ However the FS prior to the CFA injection enhanced the mechanical hyperalgesia and attenuated the expression of pCREB and ΔFosB and the acetylation of histone H3 in the IC. There was no significant difference in the numbers of ΔFosB-IR cells in the bilateral PIC between the FS+CFA and naive groups. These findings suggest neuroplasticity in the IC after the FS, which may be involved in the enhancement of CFA-induced mechanical hyperalgesia through dysfunction of the descending pain modulatory system.
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An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. ⋯ We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state.