Neuroscience
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Many patients suffer from secondary muscle hyperalgesia after experiencing angina pectoris. In this study, we examined the role of the nucleus tractus solitarius (NTS) and glutamate receptors in modulating cardiac-evoked muscle hyperalgesia induced by pericardial capsaicin, which was monitored by recording electromyogram (EMG) activity from the spinotrapezius muscle in the anesthetized rat. Unilateral chemical lesioning of the commissural NTS with the neurotoxin ibotenic acid significantly depressed the cardiac-somatic reflex; the EMG responses decreased to 56.4 ± 6.9% of that of the controls (5 of 5). ⋯ When a combination of MK-801 and MCPG was administrated, the EMG response further decreased to 22.5 ± 13.2% (n=6) of that of the controls. However, administration of a non-NMDA receptor antagonist 6, 7-dinitroquinoxaline-2, 3-dione (DNQX), at 2 and 5 nmol, had no effect on the EMG response. These results suggest that the NTS is involved in the facilitation of the cardiac-somatic reflex, and that the NMDA receptor and mGluRs play an important role in mediating this effect.
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Interleukin-10 (IL-10) has important anti-inflammatory effects and can be protective in inflammatory conditions, such as chronic pain and infection. Exploring factors that modulate IL-10 levels may provide insight into pathomechanisms of inflammatory conditions and may provide a method of neuroprotection during these conditions. Lipopolysaccharide (LPS) stimulation of astrocytes is a source of IL-10; hence, it is of interest to investigate factors that modulate this process. ⋯ Glutamate (1 mM) significantly increased LPS (1 μg/ml)-stimulated IL-10 release from astrocytes by 166% and significantly upregulated IL-10 mRNA levels. Glutamate synergistically signaled through metabotropic glutamate receptor subgroups and the phospholipase C signaling pathway. Spinal cord astrocytes may, therefore, play a larger anti-inflammatory role than first thought in situations where glutamate and a high concentration of Toll-like receptor 4 (TLR4) agonists are present.
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In the present study, the effect of medroxyprogesterone (MPA) is evaluated for its effect on pentylenetetrazole (PTZ) kindling model of epileptogenesis in mice followed by evaluation on kindling-induced changes in cognitive and motor functions. To explore whether the effects are mediated via progesterone receptors, a selective antagonist of progesterone (mifepristone, MIF) was also taken. Kindling was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks. ⋯ On grip strength test (GST) and spontaneous alternation behavior (SAB), a significant decline in GST and % alternation was observed in kindled mice which was reversed by pre-treatment with MPA. MIF, however, could reverse only the reduced % alternation and not grip strength (GS) in PTZ-kindled animals. The study shows that MPA has antiepileptogenic effects against development of PTZ-induced kindling in mice that may not be mediated via progesterone receptors.
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We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between postnatal days 3 and 15. In 11-14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity-nicotine 100 μM for in vitro studies, and epibatidine 5 μg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). ⋯ The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats.
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Comparative Study
Turning and unilateral cueing in Parkinson's disease patients with and without freezing of gait.
Freezing of gait (FOG) is one of the most disabling symptoms in Parkinson's disease (PD), and cueing has been reported to improve FOG during straight-line walking. Studies on how cueing affects FOG during turning are lacking. Given the asymmetrical nature of turning and the asymmetrical disease expression, we aimed to gain a new perspective on how unilateral cueing may alleviate FOG. ⋯ The occurrence of FOG is not influenced by turning toward the disease-dominant or nondominant side, which is confirmed by the fact that it does not make a difference at which side unilateral cueing is applied. Cueing reduces FOG during turning, but these effects disappear dramatically after cue removal. This raises further questions as to the influence of training on cue dependency and on the feasibility of either continuous application of cues or using cognitive strategies as an alternative.