Brain research
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Anandamide is a prominent member of the endocannabinoids, a group of diffusible lipid molecules which influences neuronal excitability. In this context, endocannabinoids are known to modulate certain presynaptic Ca(2+) and K(+) channels, either through cannabinoid (CB1) receptor stimulation and second messenger pathway activation or by direct action. We investigated the susceptibility of voltage-sensitive sodium channels to anandamide and other cannibimimetics using both biochemical and electrophysiological approaches. ⋯ Anandamide's action is reversible and its effects are enhanced by fatty acid amidohydrolase inhibition. We propose that voltage-sensitive sodium channels may participate in a novel signaling pathway involving anandamide. This mechanism has potential to depress synaptic transmission in brain by damping neuronal capacity to support action potentials and reducing evoked release of both excitatory and inhibitory transmitters.
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Comparative Study
Estrogen alters the bradycardia response to hypocretin-1 in the nucleus tractus solitarius of the ovariectomized female.
Experiments were performed to investigate the effect of 17beta-estradiol (E; 30 pg/ml plasma) treatment (15-25 days) in the ovariectomized (OVX) female Wistar rat on the cardiovascular responses to hypocretin-1 (hcrt-1) in the nucleus tractus solitarius (NTS). In an initial series of experiments, the distribution of hcrt-1-like immunoreactivity within the region of the NTS was mapped in both OVX only and OVX+E animals. Hcrt-1 immunoreactivity was found throughout the NTS region in both groups of females, predominantly within the caudal interstitial, commissural, medial and lateral subnuclei of the NTS. ⋯ In addition, in the OVX only animals, a few sites within the caudal commissural subnucleus of the NTS complex were found at which hcrt-1 elicited tachycardia and pressor responses. Finally, it was found that the reflex bradycardia to the activation of arterial baroreceptors as a result of increasing systemic arterial pressure with phenylephrine (2-4 microg/kg) was significantly potentiated in the OVX+E animals only. These data suggest that hcrt-1 in the NTS of the female activates a neuronal circuit that controls the circulation and that the circulating level of E alters the sensitivity of these cardiovascular circuits to hcrt-1.
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Comparative Study
Effects of transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6.
Loss of blood-brain barrier (BBB) function may contribute to post-ischemic cerebral injury by yet unknown mechanisms. Ischemia is associated with anoxia, aglycemia and loss of flow (i.e. shearing forces). We tested the hypothesis that loss of shear stress alone does not acutely affect BBB function due to a protective cascade of mechanisms involving cytokines and nitric oxide (NO). ⋯ BBB permeability did not increase during or after NNFC/reperfusion, but was increased by treatment with L-NAME or when the effects of IL-6 were blocked. Flow adapted RBMEC and astrocytes respond to NNFC/reperfusion by overproduction of IL-6, possibly secondary to increased production of NO during the reperfusion. Maintenance of BBB function during and following NNFC appears to depend on intact NO signaling and IL-6 release.
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Comparative Study
Nitric oxide in the rostral ventrolateral medulla modulates hyperpnea but not anapyrexia induced by hypoxia.
Hypoxia causes hyperpnea and anapyrexia (a regulated decrease in body temperature, T(b)) but the mechanisms involved are not well understood. The nitric oxide (NO) pathway is involved in hypoxia-induced anapyrexia and hyperpnea, but the site(s) of action is not known. Nitric oxide synthase is present in the rostral ventrolateral medulla (RVLM), which is a nucleus in the medulla oblongata involved in control of breathing, and RVLM neurons have been suggested to have intrinsic hypoxic chemosensitivity. ⋯ Typical hypoxia-induced hyperpnea and anapyrexia were observed after saline treatment. L-NMMA treatment reduced the ventilatory response to hypoxia but did not affect hypoxia-induced anapyrexia. These data suggest that nitric oxide in the RVLM is involved in the ventilatory response to hypoxia, exercising an excitatory modulation of the RVLM neurons, but plays no role in hypoxia-induced anapyrexia.
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The present study was undertaken to explore the neuronal mechanisms of hypocretin actions on neurons in the nucleus pontis oralis (NPO), a nucleus which plays a key role in the generation of active (REM) sleep. Specifically, we sought to determine whether excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the laterodorsal tegmental nucleus (LDT) and spontaneous EPSPs in NPO neurons are modulated by hypocretin. ⋯ In addition, the frequency and the amplitude of spontaneous EPSPs in NPO neurons increased following hypocretin-1 administration. These data suggest that hypocretinergic processes in the NPO are capable of modulating the activity of NPO neurons that receive excitatory cholinergic inputs from neurons in the LDT.