Neuroscience
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Enhancing the migration and phagocytosis of microglial cells is of great significance for the reducing of the risk of the neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The effect of mouse selenoprotein K (mSELENOK) on the migration and phagocytosis of BV2 microglial cells and its mechanism were studied. The results showed that the over-expression of mSELENOK can increase the migratory and phagocytic abilities of the microglial cells, while the knockdown of mSELENOK can decrease the migratory and phagocytic abilities of the cells. ⋯ Further studies revealed that selenium supplement (Na2SeO3) can increase the expression of mSELENOK in microglial cells significantly. In summary, these data suggest that mSELENOK can increase cytosolic free Ca2+ level of microglial cells by up-regulating the expression of IP3R, thus enhancing the migration and phagocytosis of microglial cells. Our results indicated that mSELENOK is an important selenoprotein, which plays a role in trace element selenium's functions and can enhance the migration and phagocytosis of microglial cells.
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In the developing brain, microglial cells play an important role in shaping neuronal circuits. These immune cells communicate with neurons through fractalkine (CX3CL1), a neuronal cytokine that acts on microglial CX3CR1 receptor. Among various functions, this signaling pathway has been implicated in the postnatal maturation of glutamatergic synapses. ⋯ In CX3CR1-deficient mice, GABAergic currents were slightly altered, whereas the developmental changes of these currents were comparable with wild-type animals. Despite these minor changes in GABAergic transmission, the GDP frequency was strikingly reduced in CX3CR1-deficient mice compared to wild-type, with no change in the GDP shape and ending period. Collectively, it emerges that, in the neonate hippocampus, the fractalkine signaling pathway tunes GDP activities and is marginally involved in the maturation of GABAergic synapses, suggesting that microglial cells have distinct impact on maturing GABAergic, glutamatergic, and network functions.
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Obesity is associated with worse neurological outcomes following overt ischemic strokes. The majority of strokes however, are covert, small strokes that often evade detection. How obesity impacts the cellular response to covert strokes is unclear. ⋯ Furthermore, there was a trend towards an increased spread of the astrogliosis scar from the infarct border in the HFD condition. Within the hypo-perfused region, significantly fewer neurons survived in HFD-fed mice than Chow-fed mice, suggesting that neurons in the HFD condition have an increased vulnerability. In summary, diet-induced obesity exacerbates covert-like stroke injuries by worsening the cellular responses in the varying levels of perfusion across the infarct.
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Low frequency stimulation (LFS) has anticonvulsant effect and may restore the ability of long-term potentiation (LTP) to the epileptic brain. The mechanisms of LFS have not been completely determined. Here, we showed that LTP induction was impaired following in vitro epileptiform activity (EA) in hippocampal slices, but application of LFS prevented this impairment. ⋯ When slices were perfused by prazosin (α1-adrenergic receptor antagonist; 10 μM) before and during LFS application, LFS improvement on LTP induction was reduced significantly. Perfusion of slices by yohimbine (α2-adrenergic receptor antagonist; 5 μM) had no effect on LFS action. Therefore, it may be concluded that following epileptiform activity, LFS can improve the impairment of LTP generation through α1, but not α2, adrenergic receptor activity.
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Activated microglia have two functional states (M1 and M2) which play dual roles in neurodegenerative diseases. In the present study, we explored a possible neuroprotective function of M2 microglia against kainic acid (KA)-induced neurodegeneration in primary neurons co-cultured with different microglial populations. Neurons were isolated from the hippocampi and cortices of C57BL/6 embryos (embryonic day 16) and microglia were extracted from neonatal pups (postnatal days 0-2). ⋯ In contrast, neurons co-cultured with M1 microglia exhibited the lowest survival rate as well as increased levels of NO and pro-inflammatory cytokines. Further, the expression of NF-κB and caspase 3 were significantly decreased in M2 microglia co-cultures compared to M1 or M0 microglia co-cultures after KA insult. Therefore, M2 microglia may exert a neuroprotective function in KA-induced neurotoxicity via the down-regulation of NF-κB and caspase 3 signaling pathways.