Neuroscience
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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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Despite the regenerative capacity of the olfactory bulb (OB), head trauma causes olfactory disturbances in up to 30% of patients. While models of olfactory nerve transection, olfactory receptor neuron (ORN) ablation, or direct OB impact have been used to examine OB recovery, these models are severe and not ideal for study of OB synaptic repair. We posited that a mild fluid percussion brain injury (mFPI), delivered over mid-dorsal cortex, would produce diffuse OB deafferentation without confounding pathology. ⋯ Robust 21 d postinjury upregulation of GAP-43 was consistent with the time course of ORN axon sprouting and synapse regeneration reported after more severe olfactory insult. Together, these findings define a cycle of synaptic degeneration and recovery at a site remote to non-contusive brain injury. We show that mFPI models diffuse ORN axon damage, useful for the study of time-dependent reactive synaptogenesis in the deafferented OB.
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Studies show that maternal consumption of a high-fat diet (HFD) can impair the formation of hypothalamic neuronal circuits in mouse offspring. This damage can be mediated by Notch1/Hes5 signaling activation, leading to repression of proneural factors such as Mash1 and Ngn2/3, which are essential for neuronal differentiation and neurogenesis. Thus, we aimed to investigate the effects of maternal HFD consumption during gestation and lactation on the Notch1/Mash1 pathway in the hypothalamus and arcuate nucleus (ARC) of mouse offspring (neonates and 28 days old). ⋯ Mash1 is important for the development of POMC and NPY neurons in the ARC. Therefore, the reduction in Mash1-labeled cells could be related to modification of the NPY neuron population in the ARC. This scenario favors hyperphagia and weight gain, and could be responsible for the development of obesity in adulthood.
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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.