Obesity is a major modifiable risk factor for Alzheimer's disease (AD), characterized by progressive atrophy of the cerebral cortex. The neurobiology of obesity contributions to AD is poorly understood. Here we show with in vivo MRI that diet-induced obesity decreases cortical volume in mice, and that higher body adiposity associates with lower cortical volume in humans. Single-nuclei transcriptomics of the mouse cortex reveals that dietary obesity promotes an array of neuron-adverse transcriptional dysregulations, which are mediated by an interplay of excitatory neurons and glial cells, and which involve microglial activation and lowered neuronal capacity for neuritogenesis and maintenance of membrane potential. The transcriptional dysregulations of microglia, more than of other cell types, are like those in AD, as assessed with single-nuclei cortical transcriptomics in a mouse model of AD and two sets of human donors with the disease. Serial two-photon tomography of microglia demonstrates microgliosis throughout the mouse cortex. The spatial pattern of adiposity-cortical volume associations in human cohorts interrogated together with in silico bulk and single-nucleus transcriptomic data from the human cortex implicated microglia (along with other glial cells and subtypes of excitatory neurons), and it correlated positively with the spatial profile of cortical atrophy in patients with mild cognitive impairment and AD. Thus, multi-cell neuron-adverse dysregulations likely contribute to the loss of cortical tissue in obesity. The dysregulations of microglia may be pivotal to the obesity-related risk of AD.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bbi.2024.04.033 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Cognition relies on transforming sensory inputs into a generalizable understanding of the world. Mirror neurons have been proposed to underlie this process, mapping visual representations of others' actions and sensations onto neurons that mediate our own, providing a conduit for understanding. However, this theory has limitations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Bochum 44780, Germany.
The novelty, saliency, and valency of ongoing experiences potently influence the firing rate of the ventral tegmental area (VTA) and the locus coeruleus (LC). Associative experience, in turn, is recorded into memory by means of hippocampal synaptic plasticity that is regulated by noradrenaline sourced from the LC, and dopamine, sourced from both the VTA and LC. Two persistent forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD) support the encoding of different kinds of spatial experience.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Protein translation is crucial for fear extinction, a process vital for adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using a Tet-On 3G genetic approach, we achieved precise temporal control over protein translation in the infralimbic medial prefrontal cortex () during fear extinction. In addition, our results reveal that the disruption of cytoplasmic polyadenylation element binding protein 1 (Cpeb1) leads to notable alterations in cell type-specific translational programs, thereby affecting fear extinction.
View Article and Find Full Text PDFIndividual choices shape life course trajectories of brain structure and function beyond genes and environment. We hypothesized that individual task engagement in response to a learning program results in individualized learning biographies and connectomics. Genetically identical female mice living in one large shared enclosure freely engaged in self-paced, automatically administered and monitored learning tasks.
View Article and Find Full Text PDFClin Neuropharmacol
January 2025
Medical Biochemistry, Erzincan Binali Yıldırım University Faculty of Medicine, Erzincan, Turkey.
Objectives: Our aim was to evaluate the comparative effects of sertraline and vortioxetine against stress-induced brain injury in rats.
Methods: The rats were assigned to a nonstress group (NSG), stress-treated control (StC), sertraline + stress (SSt), and vortioxetine + stress (VSt) groups. Sertraline and vortioxetine (10 mg/kg) were given orally by gavage to the SSt and VSt groups.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!