Neuroscience
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Effect of aging on daily rhythms of lactate metabolism in the medial prefrontal cortex of male mice.
Aging is associated with reduced amplitude and earlier timing of circadian (daily) rhythms in sleep, brain function, and behavior. We examined whether age-related circadian dysfunction extends to the metabolic function of the brain, particularly in the prefrontal cortex (PFC). Using enzymatic amperometric biosensors, we recorded lactate concentration changes in the PFC in Young (7 mos) and Aged (19 mos) freely-behaving C57BL/6N male mice. ⋯ Under constant conditions, the Aged rhythm showed a reduced amplitude not seen in the Young mice. We simultaneously observed a relationship between arousal state and PFC lactate rhythm via electroencephalography, which was modified by aging. Finally, using RT-qPCR, we found that aging affects the daily expression pattern of Glucose Transporter 1 (GLUT-1).
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Practice Guideline
Interferon-gamma facilitates neurogenesis by activating Wnt/β-catenin cell signaling pathway via promotion of STAT1 regulation of the β-catenin promoter.
Interferon-gamma (IFN-γ) is critical for central nervous system (CNS) functions and it may be a promising treatment to stimulate CNS regeneration. However, previous studies reported inconsistent results, and the molecular mechanisms remain controversial. Here we show that IFN-γ-treated mice via intraperitoneal injection have elevated IFN-γ level in central hippocampus and superior cognitive behaviors IFN-γ could activates the level of protein expression of Wnt7a, β-catenin, and CyclinD1 in Wnt/β-catenin signaling pathway of mice hippocampus. ⋯ It is also discovered firstly that Wnt/β-catenin and JAK/STAT pathways form cross-links through STAT1. Promoting neurogenesis through immune stimulation might be a promising strategy for repairing the diseased/injured CNS. This study provides a scientific basis for immunomodulation to promote nerve regeneration and offer a new therapeutic direction for central nervous system regeneration.
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Stroke is a major cause of death and long-term disability. Recent evidence suggests that hypoxia-inducible factor 1α (HIF-1α), a transcription factor that regulates oxygen levels, plays a key role in neurological outcomes after ischemic stroke. Accordingly, we investigated the mechanism of HIF-1α on pyroptotic and apoptotic cells during ischemia/reperfusion (I/R). ⋯ YC-1 significantly reduced the mRNA and protein expression of NLRP3, IL-1β, IL-18, and caspase-1; significantly decreased infarction and pyroptotic cell death after 24 h of reperfusion; attenuated the neuroinflammatory response by reducing infiltration of CD68- and MPO-positive cells after 24 h of reperfusion; and reduced apoptotic cell death following ischemic stroke. We found that HIF-1α likely regulates inflammatory responses through the NLRP3 inflammasome complex, thus influencing both apoptotic and pyroptotic cell death after stroke. These findings suggest that future investigations are needed regarding HIF-1α and its role as a potential molecular target in the treatment of acute ischemic stroke.
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Neuropeptide S (NPS) is a recently discovered peptide signalling through its receptor NPSR, which is expressed throughout the brain. Since NPSR activation increases dopaminergic transmission, we now tested if NPSR modulates behavioural and neurochemical alterations displayed by an animal model of attention-deficit/hyperactivity disorder (ADHD), Spontaneous Hypertensive Rats (SHR), compared to its control strain, Wistar Kyoto rats (WKY). NPS (0.1 and 1 nmol, intracerebroventricularly (icv)) did not modify the performance in the open field test in both strains; however, NPSR antagonism with [tBu-d-Gly5]NPS (3 nmol, icv) increased, per se, the total distance travelled by WKY. ⋯ Immunoblotting of frontal cortical extracts showed no differences of NPSR density, although SHR had a lower NPS content than WKY. SHR showed higher activity of dopamine uptake than WKY, and NPS (1 nmol, icv) did not change this profile. Overall, the present work shows that the pattern of functioning of the NPS system is distinct in WKY and SHR, suggesting that this system may contribute to the pathophysiology of ADHD.
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In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. ⋯ Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.