Neuroscience
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Inflammation aggravates the lethal consequences of intracerebral hemorrhage. Recently, many studies have found that nuclear factor-κB (NF-κB) is a crucial transcription factor that initiates inflammation in the perihematomal region of ICH. NF-κB essential modulator (NEMO)-binding domain (NBD) peptide, a cell-permeable peptide spanning the NBD of IKKα or IKKβ, functions as a highly specific inhibitor of NF-κB. ⋯ We found that NBD peptides suppressed microglia inflammation and lowered the expression of TNF-α and IL-1β in both in vivo and in vitro experiments. Further experiments were performed in mice and cultured microglia, which treated with NBD peptides in the presence of p65 siRNA confirmed that the specificity of NBD peptides inhibit ICH-induced NF-κB activation. This study demonstrated that NBD peptides exert a neuroprotective role after ICH and might be a potential candidate for a novel therapeutic strategy for ICH.
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Creatine (Cr) is a small metabolite with a central role in energy metabolism and mitochondrial function. Creatine deficiency syndromes are inborn errors of Cr metabolism causing Cr depletion in all body tissues and particularly in the nervous system. Patient symptoms involve intellectual disability, language and behavioral disturbances, seizures and movement disorders suggesting that brain cells are particularly sensitive to Cr depletion. ⋯ Moreover, our data suggest possible abnormalities of dendritic spines, synaptic function and plasticity, network excitability and neuroinflammatory response. Intriguingly, the alterations occurred in coincidence with the developmental onset of neurological symptoms. Thus, cerebral mitochondrial alterations could represent an early response to Cr deficiency that could be targeted for therapeutic intervention.
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Oscillatory activity is a prominent characteristic of the olfactory system. We previously demonstrated that beta and gamma oscillations occurrence in the olfactory bulb (OB) is modulated by the physical properties of the odorant. However, it remains unknown whether such odor-related modulation of oscillatory patterns is maintained in the piriform cortex (PC) and whether those patterns are similar between the anterior PC (aPC) and posterior PC (pPC). ⋯ Thus, some odor coding mechanisms observed in the OB are retained in the aPC. By contrast, probability of occurrence of different oscillatory patterns is homogeneous in the pPC with beta-only pattern being the most prevalent one for all the different odor families. Overall, our results confirmed the functional heterogeneity of the PC with its anterior part tightly coupled with the OB and mainly encoding odorant features whereas its posterior part activity is not correlated with odorant features but probably more involved in associative and multi-sensory encoding functions.
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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.
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Axonopathy manifested by axon swellings might constitute one of the earliest pathological features of Alzheimer's disease. It has been proposed that axonopathy might be associated with the origin of Aβ plaques. However, how axonopathy leads to Aβ plaque pathogenesis remains elusive. ⋯ Importantly, they colocalized with Aβ plaques in either the white matter or gray matter of the spinal cord at later stages, suggesting that these axonal swellings might represent the initial stages of Aβ plaque formation, and could play a role in Aβ plaque pathogenesis. Furthermore, using ultrastructural analysis we demonstrated that intracellular contents in the axonal dystrophies such as various dense vesicles leaked out into the extracellular matrix under a condition of axon swelling rupture in CST pathways of spinal cord. This provided precise structural evidence that how the Aβ leaks out from the axonal dystrophies into extracellular matrix and how an axonal swelling might serve as a nidus of amyloid plaque formation.