Neuroscience
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The involvement of the prefrontal cortex in pain processing has been recently addressed. We studied the role of the infralimbic cortex (IL) and group I metabotropic glutamate receptors (mGluRs) in descending modulation of nociception in control and monoarthritic (ARTH) conditions. Nociception was assessed using heat-induced paw withdrawal while drugs were microinjected in the IL of rats. ⋯ Finally, mGluR5 but not mGluR1 antagonists blocked the pronociceptive action of GLU in both groups. The results indicate that IL contributes to descending modulation of nociception. mGluR5 in the IL enhance nociception in healthy control and monoarthritic animals, an effect that is tonic in ARTH. Moreover, activation of IL mGluR1s attenuates nociception following the development of monoarthritis.
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Phantom hand and wrist movements in upper limb amputees are slow but naturally controlled movements.
After limb amputation, patients often wake up with a vivid perception of the presence of the missing limb, called "phantom limb". Phantom limbs have mostly been studied with respect to pain sensation. But patients can experience many other phantom sensations, including voluntary movements. ⋯ Finger extension movements appeared to be 24% faster than finger flexion movements. Neither the number of types of phantom movements that can be executed nor the kinematic characteristics were related to the elapsed time since amputation, highlighting the persistence of post-amputation neural adaptation. We hypothesize that the perceived slowness of phantom movements is related to altered proprioceptive feedback that cannot be recalibrated by lack of visual feedback during phantom movement execution.
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One common feature of most neurodegenerative diseases, including Alzheimer's disease (AD) and stroke, is the death of neuronal cells. Neuronal cell death is associated with apoptosis, generation of reactive oxygen species and oxidative stress. Neuronal cell death pathways can be reversed by endothelin B receptor agonist, IRL-1620, which was found to enhance neuroprotection by promoting vascular and neuronal growth in a rodent stroke model. ⋯ In the western blot analysis, the expression of the anti-apoptotic marker, BCL-2 was found to be increased, and that of pro-apoptotic marker, BAX was found to be decreased with liposomal IRL-1620. The effects were found to be independent of the NGF levels. Finally the free IRL-1620 was found to cause neuronal outgrowth equivalent to the 75ng/ml NGF treatment.
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Sox2 (SRY (Sex-determining region Y)-related high mobility group (HMG) box 2) is a transcription factor that serves key roles in controlling the balance between stem cells maintenance and commitment to differentiated lineages throughout the lifetime. Importantly, Sox2 deficiency results in early embryonic lethality whereas the down-regulation of Sox2 expression triggers neurodegeneration in the adult mouse brain. Moreover, Sox2 is decreased in the brain of Alzheimer's disease (AD) patients and co localizes with the β-amyloid precursor protein (βAPP) in stem cells. ⋯ In addition, we demonstrate that Sox2 is a potent activator of the non amyloidogenic processing of βAPP as shown by the Sox2-dependent augmentation of ADAM10 catalytic activity, immunoreactivity, promoter transactivation and mRNA levels with no modification of the activity and the expression of the β-secretase BACE1. Finally, the fact that γ-secretase inhibition induces an increase of ADAM10 protein levels in SH-SY5Y cells further supports the occurrence of functional AICD/Sox2/ADAM10 interactions. Altogether, our study identifies and characterizes new functional cross-talks between Sox2 and proteins involved in AD, thereby adding support to the view that Sox2 likely behaves as a protective factor during the development of this neurodegenerative disease.
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Cognitive deficits and psychotic symptoms are highly prevalent in patients with temporal lobe epilepsy (TLE). Imaging studies in humans have suggested that these comorbidities are associated with atrophy in temporal lobe structures and other limbic regions. It remains to be clarified whether TLE comorbidities are due to the frequency of spontaneous seizures or to limbic structural damage per se. ⋯ In addition to neuronal loss at several sites, we found increased parvalbumin immunostaining in the prefrontal cortex (infralimbic area), thalamus (midline and reticular nuclei), amygdala, Ammon's horn, dentate gyrus, and entorhinal cortex. These tissue changes correlated with seizure frequency and impairments in sensorimotor gating. Our work indicates that chronic seizures might impact the inhibitory-excitatory balance in the temporal lobe and its interconnected limbic regions, which could increase the likelihood of cognitive deficits and interictal psychiatric disorders.