Neuroscience
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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.
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The medial prefrontal cortex (mPFC) has been implicated in novelty detection and attention. We studied the effect of mPFC electrical stimulation on whisker responses recorded in the ventroposterior medial thalamic nucleus (VPM), the posterior thalamic nucleus (POm) and the primary somatosensory (S1) cortex in urethane anesthetized rats. Field potentials and unit recordings were performed in the VPM or POm thalamic nuclei, in S1 cortex, and in the Zona Incerta (ZI). ⋯ Facilitation was due to corticofugal projections because it was reduced after S1 cortical inactivation with lidocaine, and by activation of NMDA glutamatergic receptors because it was blocked by APV. Paired stimulation of mPFC and whiskers revealed an inhibitory effect at short intervals (<100 ms), which was mediated by ZI inhibitory neurons since PL stimulation induced response facilitation in the majority of ZI neurons (42%) and muscimol injection into ZI nucleus reduced inhibitory effects, suggesting that the mPFC may inhibit the POm neurons by activation of GABAergic ZI neurons. In conclusion, the mPFC may control the flow of somatosensory information through the thalamus by activation of S1 and ZI neurons.
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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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Oligodendrocytes (OLGs) differentiate from oligodendrocyte-precursor-cells (OPCs) for myelination in white matter. This differentiation is maintained by cell-cell interactions through trophic factors such as brain-derived-neurotrophic-factor (BDNF). However, differentiation is impaired when white matter injury occurs in a chronic cerebral hypoperfusion model. ⋯ S100B is mainly expressed by mature astrocytes, and has neuroprotective and neurotoxic effects inside and outside of cells. GFAP-positive astrocytes increased in the corpus callosum in the BCAS model, whereas the number of mature astrocytes continued to decrease, resulting in reduced BDNF. The reduction in mature astrocytes due to the discharge of S100B in ischemic conditions caused the reduction in BDNF.