Neuroscience
-
Persistent muscle pain is a common and disabling symptom for which available treatments have limited efficacy. Since tetrodotoxin (TTX) displays a marked antinociceptive effect in models of persistent cutaneous pain, we tested its local antinociceptive effect in rat models of muscle pain induced by inflammation, ergonomic injury and chemotherapy-induced neuropathy. While local injection of TTX (0.03-1μg) into the gastrocnemius muscle did not affect the mechanical nociceptive threshold in naïve rats, exposure to the inflammogen carrageenan produced a marked muscle mechanical hyperalgesia, which was dose-dependently inhibited by TTX. ⋯ TTX also displayed a robust antinociceptive effect on eccentric exercise-induced mechanical hyperalgesia in the gastrocnemius muscle, a model of ergonomic pain. Finally, TTX produced a small but significant inhibition of neuropathic muscle pain induced by systemic administration of the cancer chemotherapeutic agent oxaliplatin. These results indicate that TTX-sensitive sodium currents in nociceptors play a central role in diverse states of skeletal muscle nociceptive sensitization, supporting the suggestion that therapeutic interventions based on TTX may prove useful in the treatment of muscle pain.
-
The amygdala is a heterogeneous group of nuclei that plays a role in emotional and social learning. As such, there has been increased interest in its development in adolescent animals, a period in which emotional/social learning increases dramatically. While many mechanisms of amygdala development have been studied, the role of cell proliferation during adolescence has received less attention. ⋯ We conclude that typical neurogenesis is not a feature of the adolescent amygdala. These findings point to several possibilities, including the possibility that DCX/BrdU cells are late-developing neural precursors, or a unique subtype of NG2 cell that is relatively resistant to stress. In contrast, many proliferating OPCs are significantly impacted by a short-lived stressor, suggesting consequences for myelination in the developing amygdala.
-
Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is implicated in various pathological states in the nervous system. High-mobility group box 1 (HMGB1) is an inflammatory mediator known to be released into the local microenvironment from damaged cells. However, whether autophagy is induced and exogenous HMGB1 is involved in the process of spinal root avulsion remain unclear. ⋯ Inhibition of JNK or ERK activity significantly blocked the effect of HMGB1-induced autophagy in primary spinal neurons. Finally, HMGB1-induced autophagy increased cell viability in primary spinal neurons under oxygen-glucose deprivation conditions. The above results suggest that HMGB1 is a critical regulator of autophagy and HMGB1-induced autophagy plays an important role in protecting spinal neurons against injury, which may provide new insights into the pathophysiological process of spinal root avulsion.
-
Previous studies have indicated that sodium salicylate (SS) can cause hearing abnormalities through affecting the central auditory system. In order to understand central effects of the drug, we examined how a single intraperitoneal injection of the drug changed the level of subunits of the type-B γ-aminobutyric acid receptor (GABAB receptor) in the rat's inferior colliculus (IC). Immunohistochemical and western blotting experiments were conducted three hours following a drug injection, as previous studies indicated that a tinnitus-like behavior could be reliably induced in rats within this time period. ⋯ In contrast, no changes were observed in other brain structures such as the cerebellum. Thus, a coincidence existed between a structure-specific reduction in the level of GABAB receptor subunits in the IC and the presence of a tinnitus-like behavior. This coincidence likely suggests that a reduction in the level of GABAB receptor subunits was involved in the generation of a tinnitus-like behavior and/or used by the nervous system to restore normal hearing following application of SS.
-
Microglia are the prime cellular sources of reactive oxygen species (ROS) in the central nervous system (CNS). Chronic activation of microglia has been linked to aging-associated neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) since they produce excessive amounts of ROS for a prolonged duration leading to oxidative stress. The present study was aimed at investigating the expression and role of Sirtuin 3 (Sirt3), a protein deacetylase which is implicated in regulating cellular ROS levels. ⋯ Conversely, Sirt3 overexpression led to increase in the expression of antioxidants Cat and mnSod. Further, increase in the expression and nuclear translocation of Foxo3a was observed following Sirt3 overexpression, suggesting that Sirt3 regulates ROS by inducing the expression of antioxidants via activation of Foxo3a. The above results point to an antioxidant defense mechanism presented by Sirt3 through the activation of Foxo3a, in microglia.