Neuroscience
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High impulsivity characterizes a myriad of neuropsychiatric diseases, and identifying targets for neuropharmacological intervention to reduce impulsivity could reveal transdiagnostic treatment strategies. Motor impulsivity (impulsive action) reflects in part the failure of "top-down" executive control by the medial prefrontal cortex (mPFC). The present study profiled the complete set of mRNA molecules expressed from genes (transcriptome) in the mPFC of male, outbred rats stably expressing high (HI) or low (LI) motor impulsivity based upon premature responses in the 1-choice serial reaction time (1-CSRT) task. ⋯ Transcription factor enrichment identified mothers against decapentaplegic homolog 4 (SMAD4) and RE1 silencing transcription factor (REST) as overrepresented in the mPFC of HI rats relative to LI rats, while in silico analysis predicted a conserved SMAD binding site within the voltage-gated calcium channel subunit alpha1 E (CACNA1E) promoter region. qRT-PCR analyses confirmed that mRNA expression of CACNA1E, as well as expression of leucyl and cystinyl aminopeptidase (LNPEP), were higher in the mPFC of HI vs. LI rats. These outcomes establish a transcriptomic landscape in the mPFC that is related to individual differences in motor impulsivity and propose novel gene targets for future impulsivity research.
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Scans without evidence of dopaminergic deficit (SWEDD) patients are often misdiagnosed with Parkinson's disease (PD) but have normal dopamine transporter scans. We hypothesised that white matter tracts associated with motor and cognition functions may be affected differently by SWEDD and PD. Automatically annotated fibre clustering (AAFC) is a novel clustering method based on diffusion magnetic resonance imaging (dMRI) tractography that enables highly robust reconstruction of white matter tracts that are composed of corresponding clusters. ⋯ The support vector machine classifier achieved high accuracies in PD-NC, PD-SWEDD and NC-SWEDD classifications. This outcome validated these local white matter differences were useful to separate the three groups. These results suggest that PD exerts more significant effects on thalamo tracts than SWEDD, and unique microstructural changes occur in CB tract in SWEDD.
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Alzheimer's disease (AD) is a neuronal dementia with progressive memory loss. Amyloid-beta (Aβ) peptides has major effect in the neurodegenerative disorder, which are thought to promote mitochondrial dysfunction in AD brains. Anti-AD drugs acting upon the brain are generally difficult to develop, often cause serious side effects or lack therapeutic efficacy. ⋯ AuNPs also significantly normalizes the immunostaining of mitochondrial marker and mass in differentiated hNSCs with Aβ. The effects may be exerted by the AuNPs, as supported by its protective reversal of Aβ-induced cellular impairment and mitochondrial dysfunction in hNSCs. In fact, the results presented extend our understanding of the mechanisms through which AuNPs could exert their neuroprotective role in hNSCs treated with Aβ.
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Plexin family proteins mediate semaphorin signalling during dendritic arbour development. However, the role of PlexinA3 in the growth of dendrites of cultured cerebellar granule neurons (CGNs) is not known. We found that PlexinA3 colocalizes with CRMP2 (collapsin response mediator protein 2) in dendritic shafts. ⋯ These increases were enhanced with CRMP2 overexpression and abolished with CRMP2 knockdown, indicating that CRMP2 is the downstream effector. Furthermore, PlexinA3/CRMP2 signalling contributed to Sema3A-controlled dendritic growth. Together, these data identify a novel PlexinA3/CRMP2 pathway in semaphorin-regulated growth of cultured CGN dendrites.
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Demyelination significantly affects brain function. Several experimental methods, each inducing varying levels of myelin and neuronal damage, have been developed to understand the process of myelin loss and to find new therapies to promote remyelination. The present work investigates the effect of one such method, lysolecithin administration, on the white matter tracts in the olfactory system. ⋯ While both the LOT and AC exhibited significant demyelination at 7 dpi and had returned to control levels by 30 dpi, the process differed between the two tracts. Remyelination occurred more rapidly in the LOT: substantial recovery was observed in the LOT by 14 dpi, but not in the AC until 21 dpi. The findings indicate that (a) the LOT and AC are indeed suitable tracts for studying lysolecithin-induced de- and remyelination and (b) experimental demyelination proceeds differently between the two tracts.