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Alcohol consumption confers lasting impacts on prefrontal cortical neuron intrinsic excitability and spontaneous neurotransmitter signaling in the aging brain in mice

2 months ago
Both alcohol use disorder (AUD) and cognitive decline include disruption in the balance of excitation and inhibition in the cortex, but the potential role of alcohol use on excitation and inhibition on the aging brain is unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal...
Grace C Smith

Inhibition of an Alzheimer's disease-associated form of necroptosis rescues neuronal death in mouse models

2 months ago
Necroptosis is a regulated form of cell death that has been observed in Alzheimer's disease (AD) along with the classical pathological hallmark lesions of amyloid plaques and Tau neurofibrillary tangles. To understand the neurodegenerative process in AD, we studied the role of necroptosis in mouse models and primary mouse neurons. Using immunohistochemistry, we demonstrated activated necroptosis-related proteins in transgenic mice developing Tau pathology and in primary neurons from amyloid...
Marta J Koper

Single-cell transcriptomic and proteomic analysis of Parkinson's disease brains

2 months ago
Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex from postmortem human brains of six individuals with late-stage PD and six...
Biqing Zhu

Measurement of α-synuclein as protein cargo in plasma extracellular vesicles

2 months ago
Extracellular vesicles (EVs) are released by all cells and hold great promise as a class of biomarkers. This promise has led to increased interest in measuring EV proteins from both total EVs as well as brain-derived EVs in plasma. However, measuring cargo proteins in EVs has been challenging because EVs are present at low levels, and EV isolation methods are imperfect at separating EVs from free proteins. Thus, knowing whether a protein measured after EV isolation is truly inside EVs is...
Tal Gilboa

Maternal genetic variants in kinesin motor domains prematurely increase egg aneuploidy

2 months ago
The female reproductive lifespan is highly dependent on egg quality, especially the presence of a normal number of chromosomes in an egg, known as euploidy. Mistakes in meiosis leading to egg aneuploidy are frequent in humans. Yet, knowledge of the precise genetic landscape that causes egg aneuploidy in women is limited, as phenotypic data on the frequency of human egg aneuploidy are difficult to obtain and therefore absent in public genetic datasets. Here, we identify genetic determinants of...
Leelabati Biswas

Elucidating ATP's role as solubilizer of biomolecular aggregate

2 months ago
Proteins occurring in significantly high concentrations in cellular environments (over 100 mg/ml) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here, we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein...
Susmita Sarkar