Neuroscience
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Extracellular ATP facilitates the release of dopamine via P2 receptor activation in parts of the mesolimbic system. To characterize P2X/Y receptor subtypes in the developing dopaminergic system, their expression in organotypic slice co-cultures including the ventral tegmental area/substantia nigra (VTA/SN) complex and the prefrontal cortex (PFC) was studied in comparison to the receptor expression in 3-5 day-old and adult rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) with specific primers for the P2X(1,2,3,4,6,7) and P2Y(1) receptors in the tissue extracts of organotypic co-cultures revealed the presence of the P2X and P2Y receptor mRNAs investigated. ⋯ In the PFC of the co-cultures, and that of young but not adult rats, a number of tyrosine hydroxylase (TH)-positive cells also possessed P2Y(1)-immunoreactivity (IR). Additionally, a strong P2Y(1)-IR was observed on astrocytes. The present results show a time-, region- and cell type-dependent in vitro and in vivo expression pattern of different P2 receptor subtypes in the dopaminergic system indicating the involvement of ATP and its receptors in neuronal development and growth.
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Physical rehabilitation with endurance exercise for patients with Parkinson's disease has not been well established, although some clinical and laboratory reports suggest that exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. In this study, we used a chronic mouse model of Parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. This chronic parkinsonian model displays a severe and persistent loss of nigrostriatal neurons, resulting in robust dopamine depletion and locomotor impairment in mice. ⋯ The amphetamine-induced, dopamine release-dependent locomotor activity was markedly inhibited in the sedentary parkinsonian mice and was also inhibited in the exercised parkinsonian mice. Finally, neuronal recovery from the loss of nigrostriatal tyrosine hydroxylase expression and dopamine levels in the severe parkinsonian mice after exercise was not evident. Taken all together, these data suggest that 4 weeks of treadmill exercise promoted physical endurance, resulting in cardiorespiratory and metabolic adaptations in the chronic parkinsonian mice with severe neurodegeneration without demonstrating a restorative potential for the nigrostriatal dopaminergic function.
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The purpose of this investigation was to determine the effect of aging on neuromuscular adaptations to chronic overload. Eight young adult (8 months old) and eight aged (22 months old) Fischer 344 rats underwent unilateral synergist ablation to overload the plantaris and soleus muscles of that hindlimb and to provide control muscles from the contralateral hindlimb. Cytofluorescent staining and confocal microscopy were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs). ⋯ In contrast, myofibers of young and aged rats displayed significant (P<0.05), but similar hypertrophy ( approximately 18%) following that 4 week intervention. In both age groups, however, this hypertrophy was detected in the plantaris, but not the soleus. These data indicate that moderate aging (the equivalent of 65 years in human lifetime) does not modify the sensitivity of the neuromuscular system to chronic overload.
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Photon or near-infrared light therapy (NILT) may be an effective neuroprotective method to reduce behavioral dysfunction following an acute ischemic stroke. We evaluated the effects of continuous wave (CW) or pulse wave (P) NILT administered transcranially either 6 or 12 h following embolization, on behavioral outcome. For the studies, we used the rabbit small clot embolic stroke model (RSCEM) using three different treatment regimens: 1) CW power density of 7.5 mW/cm(2); 2) P1 using a frequency of 300 mus pulse at 1 kHz or 3) P2 using a frequency of 2 ms pulse at 100 Hz. ⋯ At the 6-h post-embolization treatment time, there was a statistically significant increase in P(50) values compared with control for both pulse P1 and P2 modes, but not the CW mode. At the 12-h post-embolization treatment time, neither the CW nor the P1 regimens resulted in statistically significant effect, although there was a trend for an improvement. The results show that P mode NILT can result in significant clinical improvement when administered 6 h following embolic strokes in rabbits and should be considered for clinical development.
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The transient receptor potential vanilloid 1 receptor (TRPV1) is an important nociceptor involved in neurogenic inflammation. We aimed to examine the role of TRPV1 in experimental colitis and in the development of visceral hypersensitivity to mechanical and chemical stimulation. Male Sprague-Dawley rats received a single dose of trinitrobenzenesulfonic acid (TNBS) in the distal colon. ⋯ JYL1421 in the post-inflammation group improved microscopic colitis and significantly decreased the VMR to CRD compared with vehicle (P<0.05, >/=30 mm Hg) but had no effect on the VMR to chemical stimulation. TRPV1 immunoreactivity in the TL and LS DRG was no different from vehicle or naïve controls. These results suggest an important role for TRPV1 channel in the development of inflammation and subsequent mechanical and chemical visceral hyperalgesia.