Neuroscience
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Multiple sclerosis (MS) is a demyelination disease that causes gradual damage to neurons. Despite the necessity of appropriate treatments at each disease stage to prevent the worsening of the damage, it is still difficult to cure MS. In this study, metabolomics and lipidomics studies were performed with time-course plasma samples (early, peak, chronic phase for MS) to elucidate the mechanism during MS progression after induction of experimental autoimmune encephalomyelitis (EAE), which is the animal model for multiple sclerosis (MS). ⋯ In particular, 26 metabolites showed significant differences at specific stages. The metabolite level of the plasma was significantly altered in response to the EAE pathogenesis, and these changes were related to inflammation status at each disease stage. This study can provide crucial information for reducing damage by differentiating treatment strategies according to disease progression.
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Addiction to prescribed opioids including oxycodone has reached tragic levels. Herein, we investigated the relevance of fibroblast growth factors (FGFs) and immediate early genes (IEGs) to withdrawal-induced incubation of drug craving following escalated oxycodone self-administration (SA). Rats were trained to self-administer oxycodone for 4 weeks. ⋯ Similarly, striatal c-fos and junB mRNA levels showed greater increases in LgA rats. The observations that fgf mRNA levels were more altered in the dorsal striatum than in the NAc of LgA rats suggest that changes in striatal FGF expression may be more salient to incubation of oxycodone craving than alterations in the NAc. Targeting FGF signaling pathways might offer novel strategies against opioid addiction.
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The dopamine D2 receptor (DRD2) and dopamine transporter (DAT) play a regulatory role in dopaminergic neurotransmission and thus play an important role in drug addiction. The prefrontal cortex (PFC), a critical part of the mesencephalic dopaminergic system, is thought to be involved in the development and maintenance of drug addiction. The addiction to ketamine is thought to induce behavioral effects primarily through actions on the central nervous system. ⋯ Additionally, neuronal changes in the PFC were examined by hematoxylin and eosin (HE) staining; the DRD2 and DAT mRNA and protein expression levels in the PFC were determined by real-time PCR and Western blot analysis, respectively. After 10-week ketamine administration, the assessment of the manifestations of toxicity in rhesus monkeys revealed significant changes in body weight and behavior, decreased DRD2 and DAT mRNA and protein expression in the PFC, and histological abnormalities including neuronal eosinophilia, pyknosis and disorderly arrangement of neurons in the PFC. These results suggest that the reduced expression of DRD2 and DAT in PFC could be involved in the behavioral and the neurological changes induced by ketamine administration, which may play an important role in the molecular mechanisms of ketamine addiction.
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Signal processing in the principal neurons of the anteroventral cochlear nucleus (AVCN) is modulated by glycinergic inhibition. The kinetics of IPSCs are specific to the target neurons. It remains unclear what glycine receptor subunits are involved in generating such target-specific IPSC kinetics in AVCN principal neurons. ⋯ To further identify the cell type-specific expression patterns of GlyRα subunits, we combined whole-cell patch clamp recording with immunohistochemistry by recording from all three types of AVCN principal neurons, characterizing the synaptic properties of their glycinergic inhibition, dye-filling the neurons, and processing the slice for immunostaining of different GlyRα subunits. We found that AVCN bushy neurons express both GlyRα1 and GlyRα4 subunits that underlie their slow IPSC kinetics, whereas both T-stellate and D-stellate neurons express only GlyRα1 subunit that underlies their fast IPSC kinetics. In conclusion, AVCN principal neurons express cell-type specific GlyRα subunits that underlie their distinct IPSC kinetics, which enables glycinergic inhibition from the same source to exert target cell-specific modulation of activity to support the unique physiological function of these neurons.