Neuroscience
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Microglia, the resident immune cells of the CNS, are known to respond to injuries, infection and inflammation in the CNS by producing proinflammatory cytokines and phagocytosing cell debris and pathogens. In this study, we investigated the expression pattern and role of dihydropyrimidinase-like 3 (Dpysl3), a member of collapsin response mediator protein family, on the inflammatory reaction of microglia. Microarray analysis comparing the global gene expression profile of ameboid and ramified microglia has shown that Dpysl3 is mainly expressed in ameboid microglia in the 5-day postnatal rat brain. ⋯ Remarkably, knockdown of Dpysl3 inhibited the migration of activated microglia coupled with deranged actin filament configuration (as revealed by F-actin cytoskeleton expression) in lamellipodia projecting from the cells. Knockdown of Dpysl3 also inhibited the phagocytic ability of activated microglia. These findings suggest that knockdown of Dpysl3 can inhibit activation, migration and phagocytic capability of microglia and consequently reduce neuroinflammation.
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Decreased survival of newborn neurons in the dorsal hippocampus after neonatal LPS exposure in mice.
Experimental studies show that inflammation reduces the regenerative capacity in the adult brain. Less is known about how early postnatal inflammation affects neurogenesis, stem cell proliferation, cell survival and learning and memory in young adulthood. In this study we examined if an early-life inflammatory challenge alters cell proliferation and survival in distinct anatomical regions of the hippocampus and whether learning and memory were affected. ⋯ Neither early (48 h after LPS) or late (33 days after LPS) proliferation of cells was affected by neonatal inflammation and neonatal LPS did not alter the behavior of young adult mice in the TFC test. These data highlight that neonatal inflammation specifically affects survival of dividing neurons and astrocytes, but not post-mitotic cells. The reduction in cell survival could be attributed to less cell survival in the dorsal hippocampus, but had no effect on learning and memory in the young adult.
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Cannabinoid CB1 receptor (CB1R) signaling system is extensively distributed in the vertebrate retina. Activation of CB1Rs regulates a variety of functions of retinal neurons through modulating different ion channels. In the present work we studied effects of this receptor signaling on K(+) channels in retinal ganglion cells by patch-clamp techniques. ⋯ WIN-induced suppression of the K(+) currents was not observed when WIN was intracellularly applied. Furthermore, an endogenous ligand of the cannabinoid receptor anandamide, the specific CB1R agonist ACEA and the selective CB2R agonist CB65 also suppressed the K(+) currents, and the effects were not blocked by AM251/SR141716 or AM630 respectively. All these results suggest that the WIN-induced suppression of the outward K(+) currents in rat retinal ganglion cells, thereby regulating the cell excitability, were not through CB1R/CB2R signaling pathways.
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Neurotransmitter release probability is related by high power to the local concentration of calcium in presynaptic terminals, which in turn is controlled by voltage-gated calcium channels. P/Q- and N-type channels trigger synaptic transmission in the majority of neurons of the central nervous system. However, whether and under which conditions both channel types act cooperatively or independently is still insufficiently understood. ⋯ Analysis of the release kinetics and the fractional release amplitude demonstrate that, whereas in only 15% of the synapses release depended exclusively on P/Q-type channels, the majority of synapses (85%) contained both N- and P/Q-type channels. Nevertheless, the kinetics of FM dye release in synapses containing both channel types was determined by the P/Q-type channels. Together, our data suggest a more direct coupling of P/Q-type channels to synaptic release compared to N-type channels, which may explain the high prevalence of neurological P/Q-type channelopathies.
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Perineuronal net (PNN) is a specialized aggregate of the extracellular matrix, which is considered to be involved in regulation of structural plasticity of neuronal circuits. Here we examined the spatial and temporal differences in Wisteria floribunda agglutinin-labeled PNN intensity in single cells in the mouse hippocampus, where the neuronal circuits engaged in cognition and emotion are embedded in the dorsal and ventral parts, respectively. In young mice, the intensity of PNN was very low, and there were no significant dorsoventral differences in all hippocampal regions. ⋯ Contrary to expectations, developmental and aging-related changes in PV intensity were not comparable to those seen in PNN intensity. The correlation coefficients between PNN and PV intensities in single cells showed gradual decline during development and aging in the CA1 and CA3 regions, while there were little correlations in the dentate gyrus regardless of age. In summary, PNNs are differentially expressed in the dorsal and ventral hippocampal circuits during development and aging, indicating their possible role for cognition and emotion control.