Neuroscience
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The progress of axonal degeneration (AxD) following injury or insult impacts both recovery from axonal transection and protection of axons from diverse insults, or axonopathy. Here we provide evidence that increases in capase-6 (Casp6) expression and action contribute to the progression of AxD. The expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing AxD was confirmed. ⋯ Following transection, morphological features of AxD were evident in both wild type and Casp6-/- mice but the latter had evidence of slowed progression. Taken together, our findings suggest a subtle but dispensable enabling role of local Casp6 expression in axons undergoing AxD. Serial analysis of cutaneous ear pinna axons in live mice provides a useful and novel model of axonal integrity.
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Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is an autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine (polyQ) tract in the ataxin-3 protein. To date, there is no effective therapy available to prevent progression of this disease. ⋯ Furthermore, experimental therapeutic strategies, including gene silencing or mutant protein clearance, mutant polyQ protein modification, stabilizing the native protein conformation, rescue of cellular dysfunction and neuromodulation to slow the progression of SCA3/MJD, have been developed. In this study, based on the current knowledge, I detail the clinical and experimental therapeutic strategies for treating SCA3/MJD, paying particular attention to drug discovery.
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The effect of cerebellar transcranial direct current stimulation (tDCS) on motor performance remains controversial. Some studies suggest that the effect of tDCS depends upon task-difficulty and individual level of task performance. Here, we investigated whether the effect of cerebellar tDCS on the motor performance depends upon the individual's level of performance. ⋯ This resulted in a significant performance improvement only for the sub-group of participants with lower performance levels as compared to that with sham-tDCS (p < 0.05). These findings suggest that the facilitation effect of cerebellar cathodal tDCS on motor skill learning of complex whole-body movements depends on the level of an individual's task performance. Thus, cerebellar tDCS would facilitate learning of a complex motor skill task only in a subset of individuals.
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Some meditation techniques teach the practitioner to achieve the state of mental silence. The aim of this study was to investigate brain regions that are associated with their volume and functional connectivity (FC) with the depth of mental silence in long-term practitioners of Sahaja Yoga Meditation. Twenty-three long-term practitioners of this meditation were scanned using Magnetic Resonance Imaging. ⋯ The capacity of long-term meditators to establish a durable state of mental silence inside an MRI scanner was associated with larger gray matter volume in a medial frontal region that is crucial for top-down cognitive, emotion and attention control. This is furthermore corroborated by increased FC of this region during the meditation-state with bilateral anterior insula/putamen, which are important for interoception, emotion, and attention regulation. The findings hence suggest that the depth of mental silence is associated with medial fronto-insular-striatal networks that are crucial for top-down attention and emotional control.
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The molecular basis for onset, maintenance and propagation of excitation along neuronal networks in epilepsy is still poorly understood. Besides different neurotransmitter receptors that control signal transfer at the synapse, one key regulator involved in all of these processes is the ATPase N-ethylmaleimide-sensitive fusion protein (NSF). Therefore, we analyzed receptor subunits and NSF levels in tissues from the medial temporal gyrus (MTG) of patients with pharmaco-resistant focal temporal lobe epilepsy resected during epilepsy surgery and autopsy controls. ⋯ We detected increased levels of NSF, NMDA 1.1, 2A and GABAAγ2 receptor subunits associated with spontaneous sharp wave spiking activity. We further identified correlations between NSF, AMPA receptor subunit, metabotropic glutamate receptor and adenosine 1 receptor levels in the spontaneous sharp wave spiking tissues. Our findings suggest that NSF plays a key role in controlling spontaneous network excitation in epilepsy by two mechanisms of action: (1) directly via controlling transmitter release at the presynaptic side, and (2) indirectly via altering the function of possible receptor crosstalk and directing/integrating specific receptor compounds through/into the postsynaptic membrane.