Neuroscience
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Ginsenoside Rg1, which could improve spatial learning and memory, might be a useful agent for preventing and treating cognitive impairment in Alzheimer's disease (AD). The present study was designed to test the neuroprotective effects of ginsenoside Rg1 on an ovariectomized (OVX) and d-galactose (d-gal)-injected rat model of AD, which is characterized with progressive learning and memory deficits, AD-related molecules alteration and differentiation/apoptosis imbalance in hippocampal neurons. OVX Wistar rats received daily injections of d-gal (100mg/kg) combined with different concentrations of ginsenoside Rg1 (5, 10, 20mg/kg) or 17-β-estradiol (E2, 100 μg/kg), or normal saline (NS, 1.0 ml/kg) for 6 weeks. ⋯ Ginsenoside Rg1 and E2-treatment increased ADAM 10 level while reduced BACE 1 level and apoptosis. Moreover, moderate i.e. 10mg/kg/d and high i.e. 20mg/kg/d ginsenoside Rg1 displayed more effective function than low i.e. 5mg/kg/d ginsenoside Rg1. Our findings demonstrate the neuroprotective effects of ginsenoside Rg1 and E2 on AD rats and support the potential application of ginsenoside Rg1 in the treatment of learning and memory impairments in postmenopausal women.
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Spinal muscular atrophy (SMA), a fatal genetic motor disorder of infants, is caused by diminished full-length survival of motor neuron (SMN) protein levels. Normally involved in small nuclear ribonucleoprotein (snRNP) assembly and pre-mRNA splicing, recent studies suggest that SMN plays a critical role in regulating apoptosis. Interestingly, the anti-apoptotic Bcl-x isoform, Bcl-xL, is reduced in SMA. ⋯ We also found that exogenous SMN expression increased full-length SMN transcripts, possibly by promoting exon 7 inclusion. Finally, co-expression of SMN and Bcl-xL produced an additive anti-apoptotic effect following PI3-kinase inhibition in SH-SY5Y cells. Our findings implicate Bcl-xL as another potential target in SMA therapeutics, and indicate that therapeutic increases in SMN may arise from modest increases in total SMN.
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We have recently reported on the efficacy of an NK1 tachykinin receptor antagonist in improving outcome following stroke, including reduced blood-brain barrier (BBB) disruption, reduced cerebral edema and improved functional outcome. The clinically approved stroke treatment, tissue plasminogen activator (tPA), has been associated with an increased risk of hemorrhage and death, if given at later time points. Accordingly, adjunctive therapies have been investigated to reduce the adverse effects of tPA and improve outcome. ⋯ BBB permeability was assessed by Evans Blue extravasation. Combination therapy of an NK1 tachykinin receptor antagonist with tPA significantly reduced BBB permeability, functional deficits and the incidence of intracerebral hemorrhage and death. As such, combined tPA-NK1 tachykinin receptor antagonist treatment may represent a novel therapeutic intervention for the treatment of reperfusion injury in acute ischemic stroke.
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The Ts65Dn (TS) mouse model of Down syndrome (DS) displays a number of behavioral, neuromorphological and neurochemical phenotypes of the syndrome. Altered GABAergic transmission appears to contribute to the mechanisms responsible for the cognitive impairments in TS mice. Increased functional expression of the trisomic gene encoding an inwardly rectifying potassium channel, subfamily J, member 6 (KCNJ6) has been reported in DS and TS mice, along with the consequent impairment in GAB Aergic function. ⋯ Also, ETH and GAB did not induce anxiety in the open field or plus maze tests, did not alter performance in the Morris water maze, and did not affect cued - or context - fear conditioning. Our results thus suggest that KCNJ6 may not be a promising drug target candidate in DS. As a corollary, they also show that long-term use of ETH and GAB is devoid of adverse behavioral and cognitive effects.
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Randomized Controlled Trial
Influence of the amount of use on hand motor cortex representation: effects of immobilization and motor training.
Converging evidence from animal and human studies has revealed that increased or decreased use of an extremity can lead to changes in cortical representation of the involved muscles. However, opposite experimental manipulations such as immobilization and motor training have sometimes been associated with similar cortical changes. Therefore, the behavioral relevance of these changes remains unclear. ⋯ No change was found for other TMS variables (motor thresholds or map location/volume/area) in either condition. In conclusion, our results indicate that a 4-day decrease, but not increase, in the amount of use of nondominant hand muscles is sufficient to induce a change in corticospinal excitability. The lack of a training effect might be explained by the use of an unspecific task (that is nevertheless representative of "real-life" training situations) and/or by insufficient duration/intensity to induce long-lasting changes.