Neuroscience
-
Vitamin D deficiency is associated with increased susceptibility to inflammatory arthritis. Sensory and sympathetic synovial nerves are critical to the development of inflammatory arthritis and spontaneously degenerate in the early phases of disease. These nerves contain vitamin D receptors and vitamin D influences nerve growth and neurotrophin expression. ⋯ In vitamin D-deficient rats, there were significant reductions in sensory nerves in the intima and sympathetic nerves in the subintima. While there was no significant change in NGF-immunoreactivity, the number of neurturin-expressing mast cells was significantly reduced in the intima, suggesting that intimal reductions in sensory nerves may be related to reductions in neurturin. Vitamin D deficiency therefore may increase susceptibility to inflammatory arthritis by depleting sensory and sympathetic synovial nerves as a result of reduced synovial neurotrophin content.
-
Stroke is a leading cause of death and morbidity worldwide, yet effective treatments are lacking. The association of prostaglandin D2 and its DP1 receptor with vasculature and blood propelled us to examine whether the clinically tested DP1 receptor agonist BW245C had beneficial effects following stroke. To determine if BW245C affects basal cerebral blood flow (CBF), C57BL/6 WT and DP1(-/-) mice were given a single i.p. injection of vehicle or BW245C, and CBF was recorded for 2h. ⋯ The significantly higher infarction volume in DP1(-/-) mice remained unchanged with BW245C treatment. Moreover, BW245C preserves hemostasis in non-stroke conditions. Combined, these data suggest that the DP1 receptor is an endogenous target that can rescue the brain following stroke by regulating CBF and hemostasis.
-
Increasing evidence indicates that Huntington's disease (HD) produces postural control impairments even before the clinical diagnosis. It has been suggested that postural disorders of HD patients are explained by deficits in the processing and integration of sensory information, but this hypothesis has been under-explored. In the present study, we evaluated the amplitude of the center of pressure (COP) displacement during maximum leaning in four directions (forward, backward, rightward and leftward) and under three sensory conditions (eyes open, eyes closed and eyes closed standing on foam). ⋯ Together, these findings demonstrate that HD reduces the limits of stability even before the clinical disease onset. Furthermore, our results indicate that dynamic postural tasks with high demand for sensorimotor integration and especially the use of proprioception are highly sensitive to early HD disease processes. This dynamic postural task may become a useful biomarker of HD progression.
-
Neuropathic pain is a chronic, refractory condition that arises after damage to the nervous system. We previously showed that an increased level of the endogenous metabolite N,N-dimethylsphingosine (DMS) in the central nervous system (CNS) is sufficient to induce neuropathic pain-like behavior in rats. However, several important questions remain. ⋯ We show that human oligodendrocytes produce DMS in culture and that the levels of DMS increase when oligodendrocytes are challenged with agents that damage white matter. These results suggest that damage to oligodendrocytes leads to increased DMS production which in turn drives inflammatory astrocyte responses involved in sensory neuron sensitization. Interruption of this pathway in patients may provide analgesia without the debilitating side effects that are commonly observed with other chronic pain therapies.
-
β-Caryophyllene (BCP), a natural bicyclic sesquiterpene present in several essential oils, displays analgesic and anti-inflammatory properties in vitro and in vivo. Astrocytes are a major class of glial cells that regulate extracellular ion balance, repair and scarring processes in the CNS following neuroinflammatory conditions and traumatic injuries. This study sought to determine the protective effect of BCP against glutamate (Glu)-induced cytotoxicity in the C6 glioma cell line on neurochemical parameters as well as their biochemical mechanism. ⋯ Moreover, BCP per se induced the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) which was reflected by improvement in the cellular GSH antioxidant system. Taken together, our results suggest that cytoprotective effects of BCP were mediated by the amelioration of cellular antioxidant responses via Nrf2 activation, which is, in part, dependent on cannabinoid receptor type 2 (CB2R) activation. This functional nonpsychoactive CB2R ligand, could represent an important molecule for protection of glial cells against oxidative stress induced by glutamate.