Brain research
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Sleep apnea is characterized by increased sympathetic activity and is associated with systemic hypertension. Angiotensin (Ang) peptides have previously been shown to participate in the regulation of sympathetic tone and arterial pressure in the hypothalamic paraventricular nucleus (PVN) neurons. We investigated the role of endogenous Ang peptides within the PVN to control blood pressure in a rat model of sleep apnea-induced hypertension. ⋯ Inhibition of PVN neurons with muscimol reversed the increase in MAP in IH rats (MUS: -9±4 mm Hg vs. vehicle +12±2 mm Hg; P<0.01). Infusion of any of the Ang antagonists also prevented the rise in MAP induced by IH (A-779: -5±1 mm Hg, losartan: -9±4 mm Hg, ZD7155: -11±4 mm Hg and PD123319: -4±3 mm Hg; P<0.01). Our results suggest that endogenous Ang peptides acting in the PVN contribute to IH-induced increases in MAP observed in this rat model of sleep apnea-induced hypertension.
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Serotonin (5-hydroxytryptamine, 5-HT) is involved in the descending modulation of nociceptive transmission in the spinal dorsal horn. The trigeminal subnucleus caudalis (Vc; medullary dorsal horn) processes nociceptive input from the orofacial region, and 5-HT-containing axons are numerous in the superficial layers of the Vc. This study examined the actions of 5-HT on the substantia gelatinosa (SG) neurons of the Vc, using gramicidin-perforated patch-clamp recording in brainstem slice preparations from immature mice. ⋯ The 5-HT-induced hyperpolarizing effects were mimicked by 8-OH-DPAT (5-HT(1A) receptor agonist) and α-methyl-5-HT (5-HT(2) receptor agonist) and blocked by WAY-100635 (5-HT(1A) receptor antagonist) and ketanserin (5-HT(2) receptor antagonist). Single-cell RT-PCR also revealed the presence of mRNA for 5-HT(1A) and 5-HT(2C) subtypes in the SG neurons. These results suggest that 5-HT acts directly on SG neurons and 5-HT-induced hyperpolarization is mediated, in part, by 5-HT(1A) receptors and 5-HT(2) receptors, as well as by the activation of K(+) channels, indicating an important role for 5-HT in the modulation of orofacial nociceptive processing at the level of the SG of the Vc in mice.
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SK-PC-B70M, an oleanolic-glycoside saponins fraction extracted from the root of Pulsatilla koreana, carries active ingredient(s) that protects the cytotoxicity induced by Aβ(1-42) in SK-N-SH cells. It was recently demonstrated that SK-PC-B70M improved scopolamine-induced deficits of memory consolidation and spatial working memory in rats, and reduced Aβ levels and plaque deposition in the brains of the Tg2576 mouse model of Alzheimer disease. In the present study, we investigated whether SK-PC-B70M produces helpful effects on the pathology of the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS). ⋯ SK-PC-B70M treatment significantly suppressed the accumulation of the by-products of lipid peroxidation, malonedialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), in the spinal cord of G93A-SOD1 mice. Moreover, histologic analysis stained with cresyl violet or anti-choline acetyltransferase (ChAT) revealed that SK-PC-B70M suppressed neuronal loss in the ventral horn of the spinal cords of G93A-SOD1 mice. These results suggest that SK-PC-B70M affords a beneficial effect on neurologic deficits of G93A-SOD1 ALS mice.
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Local perfusion of morphine produces increased levels of extracellular ascorbic acid (AA) in the nucleus accumbens (NAc) of freely moving rats. However, the pathways that regulate morphine-induced AA release in the NAc are unclear. In the present study, we used high performance liquid chromatography with electrochemical detection (HPLC-ECD) to examine the effects of intra-ventral tegmental area (VTA) administration of a GABA(A) agonist and antagonist on morphine-induced increases in AA of the NAc. ⋯ Intra-VTA infusion of bicuculline (150 ng/rat), a GABA receptor antagonist, not only abolished the enhanced extracellular AA and GABA levels produced by local perfusion of morphine but also decreased the basal release of extracellular GABA and increased the basal release of extracellular DA in the NAc. Muscimol (100 ng/rat), a GABA receptor agonist, affected the basal release of GABA and DA, but not the basal AA levels, or the morphine-induced changes in AA and GABA levels. These findings suggest that the GABA(A) receptors in the VTA play an important role in the modulation of morphine-induced AA release in the NAc, and the effect of morphine on AA release in the NAc is partially regulated by the GABA(A) receptor-mediated action of DA afferents from the VTA.
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Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of type 2 diabetes patients, however, the molecular mechanisms underlying DNP remain unclear. Emerging research implicates the participation of spinal glial cells in some neuropathic pain models. However, it remains unknown whether spinal glial cells are activated under type 2 diabetic conditions and whether they contribute to diabetes-induced neuropathic pain. ⋯ Results showed that spinal activated astrocytes dramatically increased interleukin (IL)-1β expression which may induce N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to enhance pain transmission. Together, these results suggest that spinal activated astrocytes may be a crucial component of mechanical allodynia in type 2 diabetes and "Astrocyte-IL-1β-NMDAR-Neuron" pathway may be the detailed mechanism of astrocyte-induced allodynia. Thus, inhibiting astrocytic activation in the spinal dorsal horn may represent a novel therapeutic strategy for treating DNP.