Neuroscience
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Neurokinins such as substance P and neurokinin A have long been thought to act as neurotransmitters or modulators in the nucleus tractus solitarius. However, the role and location of the receptors for these peptides have remained unclear. We examined the consequences of activation of the neurokinin-1 (NK1) receptor subtype in the rat nucleus tractus solitarius using whole-cell patch clamp recordings in brain slices. ⋯ The increase in GABA release was also shown to be protein kinase C-dependent. The data presented here show NK1 receptors in the rat nucleus tractus solitarius are present both excitatory and inhibitory neurons. Activation of these receptors can result in increases in release of both GABA and glutamate, suggesting a crucial modulatory role for NK1 receptors in the rat nucleus tractus solitarius.
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In response to cerebral ischemia, neurons activate survival/repair pathways in addition to death cascades. Activation of cyclic AMP-response-element-binding protein (CREB) is linked to neuroprotection in experimental animal models of stroke. However, a role of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MAPK/ERK or MEK), an upstream kinase for CREB, and its relation to CREB phosphorylation in neuroprotection in cerebral ischemia has not been delineated. ⋯ Similarly, animals treated with NAMDA following ischemia showed increased ERK and CREB phosphorylation in the CA1 subregion of the hippocampus during early reperfusion period with increased number of surviving neurons examined 7 days following ischemia. The NAMDA-induced neuroprotection was abolished by U0126 administered shortly after reperfusion. The results showed that the ERK-CREB signaling pathway might be involved in NAMDA-induced neuroprotection following transient global ischemia and imply that the activation of the pathway in neurons may be an effective therapeutic strategy to treat stroke or other neurological syndromes.
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Absence epilepsy is characterised by a paroxysmal loss of consciousness, of abrupt onset and termination, and is associated with a bilateral synchronous spike and wave discharge (SWD) on the electroencephalogram. Absence seizures involve an interplay between thalamic and cortical structures, although most research has so far focussed on sensory thalamic nuclei and the reticular thalamic nucleus (RTN). Thus, microinfusion of ethosuximide (ETX), a first choice anti-absence drug, into either the ventrobasal thalamus or RTN of the genetic absence epilepsy rat from Strasbourg (GAERS), a validated rat model of absence epilepsy, does not produce immediate cessation of seizure activity, as is seen following systemic administration. ⋯ No reduction of SWD was seen when ETX was infused into M1. Microinfusion of CGP 36742 (5 nmol/side), a GABA(B) antagonist, produced immediate cessation of seizure activity in both S1po and M1 and a delayed effect in S1FL. These data suggest that the ability of ETX to abolish genetically determined absence seizures is cortical-area specific and support the involvement of S1po in the initiation of SWDs.
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The pineal gland, through nocturnal melatonin, acts as a neuroendocrine transducer of daily and seasonal time. Melatonin synthesis is driven by rhythmic activation of the rate-limiting enzyme, arylalkylamine N-acetyltransferase (AA-NAT). In ungulates, AA-NAT mRNA is constitutively high throughout the 24-h cycle, and melatonin production is primarily controlled through effects on AA-NAT enzyme activity; this is in contrast to dominant transcriptional control in rodents. ⋯ This did not significantly affect the expression of ICER, AA-NAT or Cryptochrome1 in the pineal, whilst a slight suppressive effect on overall Per1 levels was observed. The attenuated response to photoperiod change appears to be specific to the ovine pineal, as the first long day induced rapid changes of Period1 and ICER expression in the hypothalamic suprachiasmatic nuclei and pituitary pars tuberalis, respectively. Overall, our data suggest a general reduction of circadian control of transcript abundance in the ovine pineal gland, consistent with a marked evolutionary divergence in the mechanism regulating melatonin production between terrestrial ruminants and fossorial rodents.
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A selective GABA(B) receptor agonist, baclofen, is known to suppress neuropathic pain. In the present study, we investigated the effect of baclofen on the excitability of trigeminal root ganglion (TRG) neurons by using the whole cell and perforated patch-clamp recording techniques. Under voltage-clamp (V(h)=-60 mV), voltage-dependent K(+) currents were recorded in the small diameter TRG neurons (<30 microm) and isolated by blocking Na(+) and Ca(2+) currents with appropriate ion replacement. ⋯ Application of baclofen reduced action potential duration evoked by a depolarization current pulse. These results indicated that activation of GABA(B) receptors inhibits the excitability of rat small diameter TRG neurons and this inhibitory action is mediated by potentiation of voltage-dependent K(+) currents. We therefore concluded that modification of nociceptive transmission in the trigeminal system by activation of GABA(B) receptors occurs at the level of small TRG neuron cell bodies and/or their primary afferent terminals, which are potential targets of analgesia by baclofen.