Neuroscience
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ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders. However, the causal relationship between ALG13 and epilepsy remains unknown. This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures. ⋯ Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice. This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice. To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
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Perceptual decisions, especially for difficult stimuli, can be influenced by choices and outcomes in previous trials. However, it is not well understood how stimulus strength modulates the temporal characteristics as well as the magnitude of trial history influence. We addressed this question using a contrast detection task in freely moving mice. ⋯ We found that more M2 neurons conveyed information about choices on the past two trials at lower than at higher contrast. Furthermore, history-trial activity in M2 was important for decoding upcoming choice at low contrast. Thus, trial history influence of perceptual choice is adaptive to the strength of sensory evidence, which may be important for action selection in a dynamic environment.
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Fatty acid binding protein 7 (FABP7) is expressed in astrocytes of the developing and mature central nervous system, and modulates astrocyte function by controlling intracellular fatty acid homeostasis. Astrocytes in the spinal cord have an important role in the process of myelin degeneration and regeneration. In the present study, the authors examined the role of FABP7 in astrocytes in a mouse model of experimental autoimmune encephalomyelitis (EAE), which is an established model of multiple sclerosis (MS). ⋯ Moreover, the area exhibiting expression of fibronectin, which is an extracellular matrix protein mainly produced by astrocytes and inhibits remyelination of oligodendrocytes, was significantly decreased in FABP7-KO compared with WT mice. Collectively, FABP7 in astrocyte may have a role to protect from the induction of inflammation leading to demyelination in CNS at early phase of EAE. Moreover, FABP7 may be involved in the regulation of fibronectin production through the modification of astrocyte activation at late phase of EAE.
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Standard treatment for Parkinson's disease (PD) is L-DOPA, but with chronic administration the majority of patients develop L-DOPA-induced dyskinesia (LID). Emerging evidence implicates the cholinergic system in PD and LID. Muscarinic acetylcholine receptors (mAChR) are known to modulate movement and of late have been implicated as possible targets for LID. ⋯ Finally, we evaluated effects of striatum- or PPN-targeted tropicamide microinfusion on LID and motor performance. Despite prior evidence, M4R blockade in either site alone did not affect the severity of LID via local striatal or PPN infusions. Taken together, these data suggest M4R as a promising therapeutic target for reducing LID using more selective compounds.
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We established hypoglycemic rat models and divided them into three groups (the sham group, the acute hypoglycemia group and the recovery group). The brain water diffusion was examined using DWI. Thereafter, neuropathologic examinations were performed in order to evaluate the distribution of brain damage. ⋯ Our work revealed that hypoglycemia significantly influenced the water diffusion of the brain. The decrease of AQP4 was associated with the formation of cytotoxic edema in acute hypoglycemia. Hypoglycemia primarily tends to damage the cerebral cortex, hippocampus and hypothalamus and may result in permanent injury to the brain.