Neuroscience
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Major depressive disorder (MDD) is characterized by severe affective as well as cognitive symptoms. Moreover, cognitive impairment in MDD can persist after the remission of affective symptoms. Theta-burst stimulation (TBS) is a promising tool to manage the affective symptoms of major depressive disorder (MDD); however, its cognition-enhancing effects are sparsely investigated. ⋯ No effects of TBS on attention and working memory were detected, supported by a moderate-to-strong level of evidence. The effects of TBS on psychomotor processing speed should be further investigated. Bilateral TBS has a substantial antidepressive effect with no immediate adverse effects on executive functions.
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Somatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer's disease and related tauopathies. Rodent primary neurons and iPSC-derived neurons are used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming, and/or require the killing of animals. ⋯ We demonstrate that the N-terminal half of TAU is not sufficient for axonal targeting, as a C-terminus-lacking construct (N-term-TAUHA) is not axonally enriched in both neuronal cell models. Importantly, SH-SY5Y-derived neurons do not show the formation of a classical axon initial segment (AIS), indicated by the lack of ankyrin G (ANKG) and tripartite motif-containing protein 46 (TRIM46) at the proximal axon, which suggests that successful axonal TAU sorting is independent of classical AIS formation. Taken together, our results provide evidence that (i) SH-SY5Y-derived neurons are a valuable human neuronal cell model for studying TAU sorting readily accessible at low cost and without animal need, and that (ii) efficient axonal TAU targeting is independent of ANKG or TRIM46 enrichment at the proximal axon in these neurons.
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The reward system plays an important role in the pathogenesis of not only drug addiction, but also diet-induced obesity. Recent studies have shown that insulin and leptin receptor signaling in the ventral tegmental area (VTA) regulate energy homeostasis and that their dysregulation is responsible for obesity and altered food preferences. Although a high-fat diet (HFD) induces inflammation that leads to insulin and leptin resistance in the brain, it remains unclear whether HFD induces inflammation in the VTA. ⋯ In experiments using these mice, Akt phosphorylation in the VTA was significantly decreased after intracerebroventricular injection of insulin, whereas no change in STAT3 phosphorylation was found with leptin. Taken together, these results suggest that HFD induces inflammation at least partly associated with microglial activation in the VTA leading to insulin resistance, independently of the energy balance. Our data provide new insight into the pathophysiology of obesity caused by a dysfunctional reward system under HFD conditions.
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Treatments promoting post-stroke functional recovery continue to be an unmet therapeutic problem with physical rehabilitation being the most reproduced intervention in preclinical and clinical studies. Unfortunately, physiotherapy is typically effective at high intensity and early after stroke - requirements that are hardly attainable by stroke survivors. The aim of this study was to directly evaluate and compare the dose-dependent effect of delayed physical rehabilitation (daily 5 h or overnight voluntary wheel running; initiated on post-stroke day 7 and continuing through day 21) on recovery of motor function in the mouse photothrombotic model of ischemic stroke and correlate it with angiogenic potential of the brain. ⋯ Western blotting and immunofluorescence microscopy experiments evaluating the expression of angiogenesis-associated proteins VEGFR2, doppel and PDGFRβ in the peri-infarct and corresponding contralateral motor cortices indicate substantial upregulation of these proteins (≥2-fold) in the infarct core and surrounding cerebral cortex in the overnight running mice on post-stroke day 21. These findings indicate that there is a dose-dependent relationship between the extent of voluntary exercise, motor recovery and expression of angiogenesis-associated proteins in this expert-recommended mouse ischemic stroke model. Notably, our observations also point out to enhanced angiogenesis and presence of pericytes within the infarct core region during the chronic phase of stroke, suggesting a potential contribution of this tissue area in the mechanisms governing post-stroke functional recovery.
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Emotion plays an important role in people's lives. However, the neural mechanism of affective perception is still unclear. In this study, steady-state visual evoked potentials (SSVEPs) were used to explore information processing speed and interactions among cortical structures involved in affective perception. ⋯ Unpleasant emotions had the fastest information processing speed in the ventral stream compared with pleasant and neutral emotions, including the middle occipital gyrus and the middle temporal gyrus, with a right hemisphere bias. In addition, unpleasant emotions were stronger than pleasant emotions in long-term causal connections in the bilateral middle temporal gyrus, and the direction was from the right hemisphere to the left hemisphere. These results provide unique insights into the cortical activities for affective perception and support the view that unpleasant emotions have priority in information perception in the middle temporal gyrus compared with pleasant and neutral emotions, with a right hemisphere bias.