Neuroscience
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Small-for-gestational age (SGA) human newborns have an increased risk of hyperphagia and obesity, as well as a spectrum of neurologic and neurobehavioral abnormalities. We have shown that the SGA hypothalamic (appetite regulatory site) neuroprogenitor cells (NPCs) exhibit reduced proliferation and neuronal differentiation. DNA methylation (DNA methyltransferase; DNMT1) regulates neurogenesis by maintaining NPC proliferation and suppressing premature differentiation. ⋯ In vivo data replicated these findings. In SGA offspring, impaired neurogenesis is epigenetically mediated, in part, via reduction in DNMT1 expression and suppression of Hes1 resulting in NPC differentiation. It is likely that the maturation of regions beyond the hypothalamus (e.g., cerebral cortex, hippocampus) may be impacted, contributing to poor cognitive and neurobehavioral competency in SGA offspring.
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Stroke is a devastating brain disorder. The pathophysiology of stroke is associated with an impaired excitation-inhibition balance in the area that surrounds the infarct core after the insult, the peri-infarct zone. Here we exposed slices from adult mouse prefrontal cortex to oxygen-glucose deprivation and reoxygenation (OGD-RO) to study ischemia-induced changes in the activity of excitatory pyramidal neurons and inhibitory parvalbumin (PV)-positive interneurons. ⋯ Disynaptic inhibitory postsynaptic currents (dIPSCs) in pyramidal neurons produced predominantly by PV-positive interneurons were reduced by OGD-RO. Following OGD-RO, dendrites of PV-positive interneurons exhibited more pathological beading than those of pyramidal neurons. Our data support the hypothesis that the differential vulnerability to ischemia-like conditions of excitatory and inhibitory neurons leads to the altered excitation-inhibition balance associated with stroke pathophysiology.
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Intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for the light signaling properties of non-image forming vision. Melanopsin-expressing ipRGCs project to retinorecipient brain regions involved in modulating circadian rhythms. Melanopsin has been shown to play an important role in how animals respond to light, including photoentrainment, masking (i.e., acute behavioral responses to light), and the pupillary light reflex (PLR). ⋯ Similar to findings in nocturnal rodents, ipRGCs were spared from significant damage but RGCs were not. Importantly, whereas image-forming vision was significantly impaired, non-image forming vision (i.e, photoentrainment, masking, and PLR) remained functional. The present study aims to characterize the resistance of ipRGCs to excitotoxicity in a diurnal rodent model.
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Spatially separated brain areas interact with each other to form networks with coordinated activities, supporting various brain functions. Interaction structures among brain areas have been widely investigated through pairwise measures. However, interactions among multiple (e.g., triple and quadruple) areas cannot be reduced to pairwise interactions. ⋯ We found that HOI strength in the macroscopic functional networks was very weak for all tasks, suggesting that major brain activities do not rely on HOIs on the macroscopic level at the timescale of hundreds of milliseconds. These weak HOIs during tasks were further investigated with a neural network model activated by external inputs, which suggested that weak pairwise interactions among brain areas organized the system without involving HOIs. Taken together, these results demonstrated the dominance of pairwise interactions in organizing coordinated activities among different brain areas to support various brain functions.
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High voltage-activated (HVA) Ca2+ (CaV) channels are oligomeric complexes formed by an ion-conducting main subunit (Cavα1) and at least two auxiliary subunits (Cavβ and CaVα2δ). It has been reported that the expression of CaVα2δ1 increases in the dorsal root ganglia (DRGs) of animals with mechanical allodynia, and that the transcription factor Sp1 regulates the expression of the auxiliary subunit. Hence, the main aim of this work was to investigate the role of Sp1 as a molecular determinant of the exacerbated expression of CaVα2δ-1 in the nerve ligation-induced model of mechanical allodynia. ⋯ Interestingly, intrathecal administration of the Sp1 inhibitor mithramycin A (Mth) prevented allodynia and decreased the expression of Sp1 and CaVα2δ-1. Likewise, electrophysiological recordings showed that incubation with Mth decreased Ca2+ current density in the DRG neurons, acting mostly on HVA channels. These results suggest that L5/L6 SNL produces mechanical allodynia and increases the expression of the transcription factor Sp1 and the subunit CaVα2δ-1 in the DRGs, while Mth decreases mechanical allodynia and Ca2+ currents through HVA channels in sensory neurons by reducing the functional expression of the CaVα2δ-1 subunit.