Brain research
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The sphenopalatine ganglia (SPG) receive their preganglionic innervation from the ventro-lateral reticular formation and nuclei of the caudal pons, and are involved in parasympathetic control of cranial glandular and vascular components including the blood supply to specific brain areas. In 53% of all SPG neurons, a particular member (MOL2.3) of the odorant receptor superfamily is co-expressed with green fluorescent protein (GFP) in MOL2.3 transgenic mouse pups. Choline acetyltransferase and vesicular acetylcholine transporter (VAChT) could be demonstrated in 90% of the GFP-positive, and 60% of the GFP-negative cells, these cells thus representing cholinergic neurons. ⋯ Inhibition of cholinergically induced intracellular calcium signalling by various omega-conotoxins indicated functional expression of alpha 3 beta 4 and alpha 7 nAChR subtypes in murine SPG cells, which could be supported by RT-PCR analysis of the neonatal mouse SPG. With regard to secondary cholinergic activation, L- but not N-subtype voltage-gated calcium channels might represent a prime target. Nicotinic signal transduction did not prove to be different in GFP-positive as compared to-negative murine SPG neurons.
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The central nucleus of the amygdala (CeA), the nociceptive amygdala, serves as the major output nucleus of the amygdala and participates in receiving and processing pain information. Considering the abundance of GABA(A) receptors in the CeA and also the attributed bidirectional roles for GABA in controlling nociception, we examined the effects of bilateral intra-CeA microinjection of a different dose of the GABA(A) receptor agonist, muscimol, and the GABA(A) receptor antagonist, bicuculline, on pain modulation using a tail-flick test. Adult rats were exposed to intra-CeA microinjection of a selective GABA(A) receptor antagonist, bicuculline, (50,100,200,400 ng/side) or a selective GABA(A) receptor agonist, muscimol, (62.5, 125,250,500 ng/side) and subjected to the tail-flick test. ⋯ Microinjection of bicuculline and muscimol into the CeA increased and decreased tail-flick latency, respectively in a dose-dependent fashion. The hyperalgesic effect of muscimol (500 ng) microinjected into the CeA was attenuated (P<0.001) by a prior microinjection of bicuculline (50 ng) at the same site. The results of the present study showed that locally released GABA in the CeA is involved in pain modulation and suggests the existence of a GABA(A) mediated inhibitory system in the CeA on pain control.
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We investigated the profile of CART immunoreactivity in some discrete hypothalamic nuclei following chronic ethanol treatment and withdrawal conditions. Adult, male, Sprague-Dawley rats were fed with liquid diet (pair-fed) or liquid diet containing ethanol (ethanol-fed) for 15 days. Thereafter, all the animals were given access to ethanol free nutritionally balanced liquid diet and killed at 0, 24, 48 and 72 h post-withdrawal, and their brains processed for immunocytochemistry using monoclonal antibodies against CART. ⋯ The immunoreactive profile in the LH, TC and DMH resembled that of the pair-fed groups at 48 and 72 h post-withdrawal intervals. However, CART-immunoreactive profile in the supraoptic nucleus did not respond to the chronic ethanol treatment and/or withdrawal. We suggest that transient up-regulation of CART in some discrete hypothalamic nuclei following ethanol withdrawal, at least in part, may contribute to the pathogenesis of ethanol withdrawal-induced symptoms like anxiety and anorexia.
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Patients with neuropathic pain present not only with persistent pain but also a complex set of additional symptoms, including mood disorders and cognitive disturbance. Given the important roles of the anterior thalamic nuclei (ATN) and anterior cingulate cortex (ACC) in the cognitive and emotional aspects of pain, investigation of the properties of ATN-ACC synapses will help us to understand the mechanisms underlying neuropathic pain. ⋯ A possible explanation for the neuropathic pain-related suppression of EPSPs is that the ACC was already sufficiently active at baseline as a result of neuropathic pain, and ATN stimulation could not further increase the already elevated level of ACC activity. This abnormal excitability of the ATN-ACC synapse may be important in understanding the mechanism underlying neuropathic pain, particularly with respect to the affective and cognitive aspects.
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Microglia activated after brain injury, are a major source of the pro-inflammatory cytokine interleukin-1 (IL-1), which is known to further exacerbate damage. However, the mechanisms that control IL-1 release in acute neuronal injury are unknown and the purpose of this study was to test the hypothesis that neuronal injury induces IL-1beta release from microglial cells. Here we report that lipopolysaccharide (LPS)-activated rat microglia co-cultured with healthy rat neurons express pro-IL-1beta, which in the absence of cell death accumulates in the cells. ⋯ This effect was reversed by the NMDA receptor antagonist MK-801, and was neuron-dependent, since NMDA had no effect on cell death or pro-IL-1beta release in mixed glial cell cultures. In addition, we show that pro-IL-1beta release from LPS-treated mixed glia or LPS-treated microglia is significantly reduced in the presence of conditioned medium from healthy co-cultures or neuronal cultures respectively. These results demonstrate that injured neurons promote the release of pro-IL-1beta from microglia, possibly by regulating microglial cell viability, and suggest an important alternative mechanism of IL-1beta release that occurs in response to neuronal injury.