Neuroscience letters
-
Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, induces apoptosis in microglia, but the underlying mechanism by which microglia apoptosis in response to VPA is not yet known. In this study, we found that the mitochondrial pathway played an important role in VPA-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. ⋯ Moreover, p38 inhibitor SB203580 strongly inhibited VPA-induced apoptosis and caspase-3 activation. Taken together, our results clearly demonstrated that VPA could induce apoptosis of microglia via p38 MAPK and mitochondrial apoptosis pathway.
-
Neuroscience letters · Sep 2010
Involvement of endogenous opioid system in scorpion toxin-induced antinociception in mice.
The present study analyzes the involvement of the endogenous opioid system in the antinociceptive effects produced in mammals after alpha- or beta- scorpion toxin injections. The analgesic effects on mice of the alpha-anatoxin Amm VIII, a weak modulator of Na(v)1.2 channel, and the depressant insect-selective beta-toxin LqqIT2 were evaluated by intraperitoneal route. The two toxins increased hot plate and tail flick latencies in a dose-dependent manner. ⋯ This increase disappeared when the toxins were co-injected with acetic acid. In conclusion, we show for the first time that an alpha-anatoxin exhibits a potent analgesic activity and confirm that depressant beta-toxins are able to reduce nociception. We hypothesize that pain relief induced by these scorpion toxins may implicate the activation of an endogenous opioid system and may be partly the result of a counter irritation phenomenon, which could be due to the activation of DNIC.
-
Neuroscience letters · Sep 2010
A central neuropathic pain model by DSP-4 induced lesion of noradrenergic neurons: preliminary report.
Neuropathic pain models are classified as central and peripheral pain models. Although various peripheral neuropathic pain models are established, central pain models are based only on spinal cord injury. DSP-4 is a competitive inhibitor of norepinephrine uptake that selectively degenerates the locus coeruleus (LC)-noradrenergic neurons projection to the cerebral cortex and hippocampus. ⋯ However, DSP-4 did not change tail-flick latency. There are significant correlations of the latency in the hot-plate test with norepinephrine contents in the cerebral cortex (r=0.432, p=0.022), the hippocampus (r=0.465, p=0.013) and the pons (r=0.400, p=0.035) but not with those in the hypothalamus and the spinal cord. As response to hot-plate and tail-flick implies supra-spinal process and spinal reflex, respectively, central neuropathic pain may be facilitated by DSP-4 depleting LC-noradrenergic neurons although the present data are preliminary.