Neuroscience
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Time perception in the millisecond and second ranges is thought to be processed by different neural mechanisms. However, whether there is a sharp boundary between these ranges and whether they are implemented in the same, overlapped or separate brain areas is still not certain. To probe the role of the right dorsolateral prefrontal cortex (dlPFC), the right supplementary motor area (SMA), and the cerebellum on time perception, we temporarily altered their activity on healthy volunteers on separate sessions using transcranial magnetic stimulation with the continuous Theta Burst Stimulation (cTBS) protocol. ⋯ We found that after cTBS in all of the studied regions, the Relative Threshold, but not the Constant Error, was affected and only when hundreds of milliseconds intervals were being categorized. Categorization of thousands of milliseconds intervals and of pitch was not affected. These results suggest that the fronto-cerebellar circuit is particularly involved in the estimation of intervals in the hundreds of milliseconds range.
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Glioblastoma (GBM) is a highly aggressive brain cancer with limited treatments and poor patient survival. GBM tumors are heterogeneous containing a complex mixture of dividing cells, differentiated cells, and cancer stem cells. It is unclear, however, how these different cell populations contribute to tumor growth or whether they exhibit differential responses to chemotherapy. ⋯ We also found a significant decrease in vimentin-positive cells, but not in Sox2 or GFAP-positive cells. However, the Sox2-positive cells significantly increased 5days after TMZ treatment. These data support that putative glioma cancer stem cells are more resistant to TMZ treatment and may contribute to tumor regrowth after chemotherapy.
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Depression induced by stress is affected by sex, age and hormonal status of the animal and also by duration and type of the stressors. Moreover, higher prevalence of depression and comorbidities in women than men implies the need to include the sex variable in studies on animal models of depression. The present study was therefore initiated to evaluate the effect of sex and ovarian hormones on depression-like phenotypes in mice exposed to a 21-day Chronic Variable Mild Stress (CVMS) paradigm. ⋯ There was a significant decrease in the BDNF protein expression along with an increase in the mRNA expression of CRH, NR3C1, CART, and NPY in intact females, but not in the other two groups of mice. OVX females resembled males in behavioral and molecular responses to CVMS. 17β-Estradiol (E2) administration, not Progesterone (P4), to OVX female stress mice, mitigated despair and enhanced hedonic capacity with an increased expression of BDNF in PFC. This study strengthens the evidence for the beneficial effects of E2 administration in stress condition.
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From a view point of the glutamate excitotoxicity theory, several studies have suggested that abnormal glutamate homeostasis via dysfunction of glial glutamate transporter-1 (GLT-1) may underlie neurodegeneration in amyotrophic lateral sclerosis (ALS). However, the detailed role of GLT-1 in the pathogenies of ALS remains controversial. To assess this issue, here we elucidated structural alterations associated with dysregulation of glutamate homeostasis using SOD1(G93A) mice, a genetic model of familial ALS. ⋯ Interestingly, the coverage of α-motoneurons by VGluT2(+) presynaptic terminals was transiently increased at 9weeks of age, and then gradually decreased towards 21weeks of age. On the other hand, there were no time-dependent alterations in the coverage of α-motoneurons by GABAergic presynaptic terminals. These findings suggest that VGluT2 and GLT-1 may be differentially involved in the pathogenesis of ALS via abnormal glutamate homeostasis at the presymptomatic stage and end stage of disease, respectively.
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Pain is a common complication of herpes zoster (HZ) infection which results from reactivation of a latent varicella zoster virus (VZV). A third of HZ patients' progress to a chronic pain state known as post herpetic neuralgia (PHN), and about a quarter of these patients' have orofacial pain. The mechanisms controlling the pain responses are not understood. ⋯ VZV-induced nociception was significantly decreased after administering CNO in male rats. Nociception significantly increased concomitant with increased thalamic c-fos expression after attenuating thalamic VGAT expression. These data establish that the lateral thalamus (posterior, ventral posteromedial, ventral posterolateral and/or reticular thalamic nucleus) controls VZV-induced nociception in the orofacial region, and that GABA in this region appears to reduce the response to VZV-induced nociception possibly by gating facial pain input.