Neuroscience
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Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. ⋯ We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration.
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Prolonged use/abuse of opioid agonists leads to development of severe dependence to these drugs. Orexin-A has a crucial role in development of morphine dependence. The locus coeruleus (LC) is implicated in the expression of morphine withdrawal signs. ⋯ Chronic morphine injection induced morphine dependence in LC neurons which was revealed as a significant increase in LC neuronal firing rate in response to naloxone. The results of this study indicated that SB-334867 administration prior to each morphine injection prevents naloxone-elicited neuronal activation within the LC. In addition, naloxone injection enhanced the cAMP concentration in LC neurons of morphine-dependent animals and this effect was significantly reduced by OX1R blockade.
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Clinical Trial
Short inter-stimulus intervals can be used for olfactory electroencephalography in patients of varying olfactory function.
Use of chemosensory event-related potentials (ERPs) is limited by relatively poor signal-to-noise ratios (SNRs). We hypothesized that by reducing the standard inter-stimulus interval (ISI), the increased number of trial repetitions possible may increase SNR. In order to further investigate this, we performed the largest study to date assessing chemosensory ERP using short and long ISIs in 101 participants of varying olfactory function. ⋯ We also demonstrated significantly increased SNR using short PEA-ISIs, in the normosmic and functionally anosmic groups. Comparing between groups of different olfactory function, hyposmic patients achieved faster onsets and greater amplitudes than normosmics under the PEA-10s protocol. This could be due to increased stimulus attendance, but requires confirmation with further research.
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Patients sometimes complain that non-vital teeth after root canal treatment (RCT) are paresthesia compared with vital teeth, and previous psychological studies on the tactile sensibility of non-vital teeth remained controversial. In the present study, intrinsic signal optical imaging, which served as an objective tool, was employed to compare the cortex response characteristics following forces applied to the cat non-vital and vital canines. Based on the evoked cortical responses, the response threshold, signal strength, spatial pattern, temporal dynamics and the preference of force direction, they were not significantly different between vital and non-vital canines. It seemed that the tactile sensibility of vital and non-vital teeth was comparable at the cortical response level, and pulpal receptors were not concerned in tactile function.
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Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. ⋯ Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.