Neuroscience
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Early degeneration of pedunculopontine nucleus (PPN) is considered part of changes that characterize premotor stages of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN in motor execution and in the development of oxidative stress events in striatal and nigral tissues in rats were evaluated. The motor performance was assessed using the beam test (BT) and the cylinder test (CT). ⋯ This significant increase of CAT EA persisted in the nigral tissue (p<0.001) and reached the striatal tissue (p<0.001) seven days after PPN injury. Also at seven days post-injury PPN, increased concentrations of MDA (p<0.01) and a tendency to decrease in the concentrations of NO in both structures (SNpc and striatum) were found. The events associated with the generation of free radicals at nigral and striatal levels, can be part of the physiological mechanisms underlying motor dysfunction in rats with unilateral PPN neurotoxic lesion.
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Necrostatin-1 (Nec-1) is an inhibitor of necroptosis, playing an important role in inhibition of pathological death in the central nervous system (CNS). Our earlier study suggests that Nec-1 protects the injured spinal cord. In this study, we found that Nec-1 reduces the elevated Ca(2+) concentration in mitochondria post-injury and preserves the remarkably decreased mitochondrial membrane potential (MMP) level post-spinal cord injury (SCI). ⋯ It also inhibits the up-regulation of mitochondrial fusion genes Mnf1, Mnf2 within 6h post-injury and adjusts the abnormal expression of mitochondrial fission gene Fis1. All these results indicate the improvement of mitochondrial functions in injured spinal cord after the treatment of Nec-1. This research revealed the mechanisms of functional protection of Nec-1 by mitigating mitochondrial dysfunction post-SCI.
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The present study examines the change in water diffusion properties of the corpus callosum (CC) and the hippocampus, in response to prolonged hypobaric hypoxia (HH) stress, using in vivo magnetic resonance imaging (MRI) modalities such as T2 relaxometry and diffusion tensor imaging (DTI). Three groups of rats (n=7/group) were exposed to a simulated altitude of 6700m above sea level for the duration of 7, 14 and 21days, respectively. Data were acquired pre-exposure, post-exposure and after 1week of normoxic follow-up in each group. ⋯ Interestingly, 21-day HH-exposed rats did not show change in ADC values. The decrease in T2 values after 14 and 21days in the hippocampal region depicts iron deposition, which was confirmed by histopathology. This study successfully demonstrated the use of MRI modality to trace water diffusion changes in the brain due to prolonged HH exposure.
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Oxytocin (OT) plays an important role in pain modulation and antinociception in the central nervous system. However, little is known about its peripheral effects. This study was conducted to investigate the effect of OT on the electrical properties of neurons in the dorsal root ganglia (DRG) and the underlying mechanisms. ⋯ OT produced a concentration-dependent increase in intracellular Ca(2+) in DRG neurons that responds to capsaicin, which can be attenuated by atosiban, but not by NPLA. OT-evoked membrane hyperpolarization and increase of outward current were distinctly attenuated by glibenclamide, a blocker of ATP-sensitive K(+) (KATP) channel. OT might be an endogenous antinociceptive agent and the peripheral antinociceptive effects of OT are mediated by activation of the Ca(2+)/nNOS/NO/KATP pathway in DRG neurons.
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Nuclear hormone receptor coregulator-interacting factor 1 (NIF-1) is a zinc finger nuclear protein that was initially identified to enhance nuclear hormone receptor transcription via its interaction with nuclear hormone receptor coregulator (NRC). NIF-1 may regulate gene transcription either by modulating general transcriptional machinery or remodeling chromatin structure through interactions with specific protein partners. We previously reported that the cytoplasmic/nuclear localization of NIF-1 is regulated by the neuronal Cdk5 activator p35, suggesting potential neuronal functions for NIF-1. ⋯ Furthermore, activity-induced Ca(2+) influx, which is critical for neuronal morphogenesis, stimulated the nuclear localization of NIF-1 in cortical neurons. Suppression of NIF-1 expression reduced the up-regulation of neuronal activity-dependent gene transcription. These findings collectively suggest that NIF-1 directs neuronal morphogenesis during early developmental stages through modulating activity-dependent gene transcription.