Network dysfunction precedes neurodegeneration in a dox-regulatable TDP-43 mouse model of ALS-FTD.

Neuronal hyperexcitability is a hallmark of amyotrophic lateral sclerosis (ALS) but its relationship with the TDP-43 aggregates that comprise the predominant pathology in over 90% of ALS cases remains unclear. Emerging evidence indicates that TDP-43 pathology induces neuronal hyperexcitability, which may contribute to excitotoxic neuronal death. To characterize TDP-43 mediated network excitability changes in a disease-relevant model, we performed in vivo continuous electroencephalography monitoring and ex vivo acute hippocampal slice electrophysiology in rNLS8 mice (males and females), which express human TDP-43 with a defective nuclear localization signal (hTDP-43ΔNLS).

SIV infection induces alterations in gene expression and loss of interneurons in Rhesus Macaque frontal cortex during early systemic infection.

Understanding the neurobiological mechanisms underlying HIV-associated neurocognitive decline in people living with HIV is frequently complicated by an inability to analyze changes across the course of the infection and frequent presence of comorbid psychiatric and substance use disorders. Preclinical non-human primate simian immunodeficiency virus (SIV) models help address these shortcomings. However, SIV studies frequently target protracted endpoints, limiting our understanding of the neuromolecular alterations during the early post-infection window.

Detection of sex-specific glutamate changes in subregions of hippocampus in an early-stage Alzheimer's disease mouse model using GluCEST MRI.

Introduction: Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high-resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex-specific manner.

Methods: Eight-month-old male and female AD mice harboring mutant amyloid precursor protein (APP: n = 36) and wild-type (WT: n = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (H-MRS) in hippocampus and thalamus/hypothalamus using 9.

Early-stage mapping of macromolecular content in APP mouse model of Alzheimer's disease using nuclear Overhauser effect MRI.

Non-invasive methods of detecting early-stage Alzheimer's disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be altered in Alzheimer's pathology, with early disruptions in cell membrane integrity and signaling pathways leading to the buildup of amyloid-beta plaques and neurofibrillary tangles.

In vivo assessment of β-hydroxybutyrate metabolism in mouse brain using deuterium ( H) MRS.

Purpose: To monitor the metabolic turnover of β-hydroxybutyrate (BHB) oxidation using H-MRS in conjunction with intravenous administration of H labeled BHB.

Methods: Nine-month-old mice were infused with [3,4,4,4]- H -BHB (d -BHB; 3.11 g/kg) through the tail vein using a bolus variable infusion rate for a period of 90 min.

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space.

Models of hypoxia and ischemia-induced seizures.

Despite greater understanding and improved management, seizures continue to be a major problem in childhood. Neonatal seizures are often refractory to conventional antiepileptic drugs, and can result in later life epilepsy and cognitive deficits, conditions for which there are no specific treatments. Hypoxic and/or ischemic encephalopathy (HIE) is the most common cause for neonatal seizures, and accounts for more than two-thirds of neonatal seizure cases.

High copy wildtype human 1N4R tau expression promotes early pathological tauopathy accompanied by cognitive deficits without progressive neurofibrillary degeneration.

Introduction: Accumulation of insoluble conformationally altered hyperphosphorylated tau occurs as part of the pathogenic process in Alzheimer's disease (AD) and other tauopathies. In most AD subjects, wild-type (WT) tau aggregates and accumulates in neurofibrillary tangles and dystrophic neurites in the brain; however, in some familial tauopathy disorders, mutations in the gene encoding tau cause disease.

Results: We generated a mouse model, Tau4RTg2652, that expresses high levels of normal human tau in neurons resulting in the early stages of tau pathology.

Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging.

Calcium imaging is a versatile experimental approach capable of resolving single neurons with single-cell spatial resolution in the brain. Electrophysiological recordings provide high temporal, but limited spatial resolution, because of the geometrical inaccessibility of the brain. An approach that integrates the advantages of both techniques could provide new insights into functions of neural circuits.