Neuroscience
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Chronic psychogenic stress can increase neuronal calcium influx and generate the intracellular accumulation of oxidative (ROS) and nitrosative (RNS) reactive species, disrupting synaptic transmission in the brain. These molecules impair the Na,K-ATPase (NKA) activity, whose malfunction has been related to neuropsychiatric disorders, including anxiety, depression, schizophrenia, and neurodegenerative diseases. In this study, we assessed how 14 days of restraint stress in rats affect NKA activity via oxidative/nitrosative damage in the frontal cortex (FCx), a crucial region for emotional and cognitive control. ⋯ No cellular death or neurodegeneration was observed in the FCx of S14 + 1d animals. Pharmacological inhibition of iNOS or COX-2 before each stress session prevented lipid peroxidation and the α2,3-NKA activity loss. Our results show that repeated restraint exposure for 14 days decreases the activity of α2,3-NKA in FCx 24 h after the last stress, an effect associated with augmented inflammatory response and oxidative and nitrosative damage and suggest new pathophysiological roles to neuroinflammation in neuropsychiatric diseases.
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Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder and is characterized by loss of dopaminergic neurons. Biomarkers for tracking disease progression are useful indicators of the pathological conditions or the effects of therapeutic interventions on disease progression, but there are currently no known biomarkers in the blood that correlate with the progression of PD. Several studies have suggested that exosomes reflect intracellular changes that occur in response to pathological conditions and are an effective source of biomarkers for disease progression. ⋯ Fibrinogen gamma chain in plasma was also decreased in PD patients at HY stages II and III compared to healthy subjects. Therefore, these three exosomal proteins (clusterin, complement C1r subcomponent, and apolipoprotein A1) and fibrinogen gamma chain in plasma may be biomarker candidates for the diagnosis of PD. In particular, the expression levels of apolipoprotein A1 in exosomes may be useful for tracking the progression of PD.
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Although opioid addiction has risen dramatically, the role of gender in addiction has been difficult to elucidate. We previously found sex-dependent differences in the hippocampal opioid system of Sprague-Dawley rats that may promote associative learning relevant to drug abuse. The present studies show that although female and male rats acquired conditioned place preference (CPP) to the mu-opioid receptor (MOR) agonist oxycodone (3 mg/kg, I. ⋯ In dentate hilar GABAergic dendrites that contain neuropeptide Y, Sal-females compared to Sal-males had higher plasmalemmal DORs, and near-plasmalemmal DORs increased in Oxy-females. This redistribution of MORs and DORs within hilar interneurons in Oxy-females would potentially enhance disinhibition of granule cells via two different circuits. Together, these results indicate that oxycodone CPP induces sex-dependent redistributions of opioid receptors in hippocampal circuits in a manner facilitating opioid-associative learning processes and may help explain the increased susceptibility of females to opioid addiction acquisition and relapse.
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The present study examined corticospinal excitability of the contralateral and ipsilateral hemispheres during actual (ACT) and imaginary (IMG) unilateral hand force-matching tasks of different difficulty. Seventeen young male adults (21.2 ± 2.2 yrs) actually and imaginarily matched their left index finger abduction force to a displayed target force. Task difficulty was manipulated by varying the acceptable force range about each mean target force (5 and 15% MVC for ACT, 15% MVC for IMG). ⋯ The relative change in MEP amplitude in the right hand from EASY to DIFF in ACT was positively correlated (r = 0.63) with that in IMG. These results indicate that greater task difficulty increases corticospinal excitability of the contralateral hemisphere in ACT, and increases corticospinal excitability of the ipsilateral hemisphere in both ACT and IMG. The relative changes in corticospinal excitability of the ipsilateral hemisphere with increasing task difficulty are correlated between ACT and IMG.
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Recent electrophysiological studies in animals using oddball stimuli have demonstrated that neurons along the auditory pathway from the inferior colliculus to the auditory cortex (AC) have a strong response to rarely presented stimuli. This phenomenon is termed stimulus-specific adaptation (SSA), which is regarded as novelty detection. However, in the medial geniculate body (MGB), it is not clear whether SSA is frequency dependent or if neurons in the MGB are sensitive to the regularity of the stimuli. ⋯ It was found MGB neurons exhibited strong SSA when the pure-tone stimulus of the oddball stimulus deviated far from the characteristic frequency, even in the ventral region of the MGB, suggesting that the MGB may contribute to SSA in the primary AC. Moreover, we found the neuronal population in the MGB was sensitive to high-order sound structure, where deviant responses were smaller and standard responses were stronger for irregular oddball stimuli. We conclude that regularity detection occurs in the MGB, but in a manner distinct from the AC.