Neuroscience
-
Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that sevoflurane has neuroprotective effects against ischemic stroke, but its effects on ischemia-induced formation of astrogliosis and glial scar are unknown. ⋯ In order to confirm whether inhibition of cathepsin B could attenuate the formation of glial scar, we used cathepsin B inhibitor CA-074Me as a positive control. The results showed that inhibition of cathepsin B could decrease the expression of GFAP, neurocan and phosphacan. Taken together, sevoflurane postconditioning can attenuate astrogliosis and glial scar formation after ischemic stroke, associating with inhibition of the activation and release of lysosomal cathepsin B.
-
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.
-
Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. ⋯ Analysis of these subpopulations revealed that DLS MSNs with more primary dendrites were selectively remodeled by chronic nicotine exposure and remodeling was specific to the distal-most portions of the dendritic arbor. Co-administration of the dopamine D1 receptor (D1R) antagonist SCH23390 completely reversed the selective effects of nicotine on DLS MSN dendrite morphology, supporting a causal role for dopamine signaling at D1 receptors in nicotine-induced dendrite restructuring. Considering the functional importance of the DLS in shaping and expressing habitual behavior, these data support a model in which nicotine induces persistent and selective changes in the circuit connectivity of the DLS that may promote and sustain addiction-related behavior.
-
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.
-
Chondroitin sulfate proteoglycans (CSPGs) are axon growth inhibitors in the glial scar, and restrict axon regeneration following damage to the adult mammalian central nervous system. CSPGs have recently been identified as functional ligands for Nogo receptor-1 (NgR1), which is the common receptor for Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and B lymphocyte stimulator (BLyS). We have previously reported that through its binding to NgR1, lateral olfactory tract usher substance (LOTUS) suppresses Nogo, MAG, OMgp, and BLyS-induced axon growth inhibition. ⋯ LOTUS overexpression rescued CSPG-induced growth cone collapse and neurite outgrowth inhibition in cultured dorsal root ganglion neurons, which only weakly express endogenous LOTUS. In cultured olfactory bulb neurons, which endogenously express LOTUS, the growth cone was insensitive to CSPG-induced collapse, but was sensitive to collapse induced by CSPGs in lotus-deficient mice. Our data demonstrate that LOTUS suppresses CSPG-induced axon growth inhibition, suggesting that LOTUS may represent a promising therapeutic agent for promoting axon regeneration.