Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 27, 2024

Abstract Background Traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s disease (AD), and accumulating evidence supports role adaptive immune B T cells in both TBI AD pathogenesis. We previously identified cell major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive expansion after TBI. also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII acutely reduced + splenic was neuroprotective. The current study investigated chronic effects 5xFAD mouse model, with without Methods 12-week-old male wild type (WT) mice were administered either antagonist (CAP) or vehicle, once at 30 min sham lateral fluid percussion (FPI). Analyses included flow cytometric analysis dural meninges spleen, histopathological brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, assessment motor neurobehavioral function over ensuing 6 months. Results 9-month-old had significantly more compared age-matched WT mice. A one-time treatment CAP this population Importantly, improved some immune, histopathological, impairments six Although FPI did not further elevate meningeal cells, it negate ability reduce 3 months age exacerbated aspects pathology mice, including reducing hippocampal neurogenesis, increasing plaque deposition CA3, altering microgliosis, disrupting structure. ameliorated but all these effects.

Language: Английский

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An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for pathogenesis Aβ affect balance in chemical neurotransmitters brain. Thus, current review examined role discusses alterations neurochemical activity cross talk with their receptors transporters. In presence tangles, changes may occur expression neuronal which turn triggers excessive release glutamate into synaptic cleft contributing to cell death damage. GABAergic system also be affected by AD pathology similar way. addition, decreased cholinergic dysfunction dopamine neurotransmission contribute damage cognitive function. Moreover, deficiencies noradrenergic neurons within locus coeruleus suggests that stimulation could useful addressing its pathophysiology. regulation melatonin, known effectiveness enhancing function preventing accumulation, along involvement serotonergic histaminergic cognition memory, becomes remarkable promoting AD. Additionally, nitric oxide adenosine-based therapeutic approaches play protective neuroinflammation. Overall, neurotransmitter-based strategies emerge as pivotal neurotransmitter homeostasis context This discussed potential drugs effective slowing correcting processes targeting imbalance Therefore, serve future strategy tackle

Language: Английский

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Preserved blood-brain barrier and neurovascular coupling in female 5xFAD model of Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: May 5, 2023

Dysfunction of the cerebral vasculature is considered one key components Alzheimer's disease (AD), but mechanisms affecting individual brain vessels are poorly understood.Here, using in vivo two-photon microscopy superficial cortical layers and ex imaging across regions, we characterized blood-brain barrier (BBB) function neurovascular coupling (NVC) at level adult female 5xFAD mice, an aggressive amyloid-β (Aβ) model AD.We report a lack abnormal increase adsorptive-mediated transcytosis albumin preserved paracellular for fibrinogen small molecules despite extensive load Aβ. Likewise, NVC responses to somatosensory stimulation were all regulatory segments microvasculature: penetrating arterioles, precapillary sphincters, capillaries. Lastly, Aβ plaques did not affect density capillary pericytes.Our findings provide direct evidence microvascular mice highlight critical dependence experimental outcomes on choice preclinical models AD. We propose that presence parenchymal does warrant BBB dysfunction generalized view impairment inherent aggregation may need be revised.

Language: Английский

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Disrupted astrocyte-neuron signaling reshapes brain activity in epilepsy and Alzheimer’s disease

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Correlations of blood and brain NMR metabolomics with Alzheimer’s disease mouse models

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 18, 2025

Alzheimer's disease (AD) is a complex, progressive neurodegenerative disorder, impacting millions of geriatric patients globally. Unfortunately, AD can only be diagnosed post-mortem, through the analysis autopsied brain tissue in human patients. This renders early detection and countering progression difficult. As progresses, metabolomic profile other organs change. These alterations detected peripheral systems (i.e., blood) such that biomarkers identified monitored with minimal invasion. In this work, High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy used to correlate biochemical changes mouse tissues, from cortex hippocampus, blood plasma. Ten micrograms each ten microliters plasma were obtained 5XFAD Tg mice models (n = 15, 8 female, 7 male) female C57/BL6 wild-type 8). Spectral regions-of-interest (ROI, n 51) identified, 121 potential metabolites assigned using Human Metabolome Database tabulated according their trends (increase/decrease, false discovery rate significance). work several impact glucose oxidation (lactic acid, pyruvate, glucose-6-phosphate), allude oxidative stress resulting dysfunction (L-cysteine, galactitol, propionic acid), as well those interacting neural pathways (taurine, dimethylamine). also suggests correlated within plasma, proposing an avenue for biomarker detection, ideally leading improved patient diagnosis prognosis future.

Language: Английский

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