Neuroscience
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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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Prescription opioid abuse, for example of oxycodone, is a pressing public health issue. This study focuses on how chronic oxycodone self-administration (SA) affects the reward pathways in the mouse brain. In this study, we tested the hypothesis that the expression of reward-related genes in the ventral and dorsal striatum, areas involved in different aspects of opioid addiction models, was altered within 1 h after chronic oxycodone SA, using transcriptome-wide sequencing (RNA-seq). ⋯ Some genes detected by RNA-seq were confirmed by quantitative polymerase chain reaction (qPCR). Conclusion: A RNA-seq study shows that chronic oxycodone SA alters the expression of several reward-related genes in the dorsal and ventral striatum. These results suggest potential mechanisms underlying neuronal adaptation to chronic oxycodone self-exposure, of relevance to our mechanistic understanding of prescription opioid abuse.
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Pathological Tau (P-Tau) leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. The P301L transgenic mice well mimic human tauopathy features; P-Tau localizes also at the dendritic spine level and this correlates with synaptic markers down-regulation. Importantly, tg females present a more severe pathology compared to male mice. ⋯ These results suggest that JNK plays a key role in synaptopathy of P301L mice. Importantly, until now, there are any efficient treatments against synaptic pathology and JNK could represent an interesting target to tackle P-Tau-induced synaptic pathology. It will be important to test specific JNK inhibitors to verify their potential neuroprotective effect.
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Visual-related cortex plays an important role in the process of movement. It is of great importance to clarify whether traumatic spinal cord injury (SCI), which is a typical disease that results in sensorimotor dysfunction, leads to the alteration of visual-related brain structure and function area. To address this issue, multimodality MRI was applied on eleven patients with acute incomplete cervical cord injury (ICCI) and eleven healthy controls (HCs) to explore possible structural and functional changes of the brain. ⋯ Moreover, ICCI patients exhibited decreased intra-network functional connectivity (FC) in the medial vision network (mVN). The mean fALFF value was correlated with clinical motor scores of the left extremities and the total motor scores. Our findings proved that ICCI can not only cause structural changes in visual-related brain regions, but also result in visual-related brain functional alterations, revealing the possible mechanism of the effects of visual feedback training in motor function rehabilitation of SCI patients.
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Cellular communication through chemical synapses is determined by the nature of the neurotransmitter and the composition of postsynaptic receptors. In the excitatory synapse between bipolar and ganglion cells of the retina, postsynaptic AMPA receptors mediate resting activity. During evoked response, however, more abundant and sustained levels of glutamate also activate GluN2B-containing NMDA receptors (NMDARs). ⋯ Surprisingly, this activity was driven primarily by atypical activation of GluN2A -containing NMDARs, not GluN2B-NMDARs. Indeed, immunohistochemical analyses and Western blot showed greater levels of the GluN2A-NMDAR subunit expression in rd10 retina compared to wild type. Overall, these results demonstrate how aberrant signaling leads to pathway-specific alterations in NMDAR expression and function.