Social isolation impairs cognition via Aβ-mediated synaptic dysfunction.

Social isolation impairs cognition via Aβ-mediated synaptic dysfunction.

Publication date: Sep 18, 2024

Social isolation (SI) is a common phenomenon in the modern world, especially during the coronavirus disease 2019 pandemic, and causes lasting cognitive impairments and mental disorders. However, it is still unclear how SI alters molecules in the brain and induces behavioural dysfunctions. Here, we report that SI impairs cognitive function and induces depressive-like behaviours in C57BL/6 J mice, in addition to impairing synaptic plasticity and increasing the levels of APP cleavage-related enzymes, thereby promoting Aβ production. Moreover, we show that in APP/PS1 transgenic mice, SI accelerates pathological changes and behavioural deficits. Interestingly, downregulation of the expression of the BACE1 attenuates SI-induced Aβ toxicity and synaptic dysfunction. Furthermore, early intervention with BACE1 shRNA blocks SI-induced cognitive impairments. Together, our data strongly suggest that SI-induced upregulation of BACE1 expression mediates Aβ toxicity and induces behavioural deficits. Down-regulation of BACE1 may be a promising strategy for preventing SI-induced cognitive impairments.

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Concepts Keywords
Coronavirus Amyloid beta-Peptides
Enzymes Amyloid beta-Peptides
Mice Amyloid beta-Protein Precursor
Pandemic Amyloid beta-Protein Precursor
Psychiatry Animals
Aspartic Acid Endopeptidases
Aspartic Acid Endopeptidases
Bace1 protein, mouse
Cognitive Dysfunction
COVID-19
Disease Models, Animal
Male
Mice
Mice, Transgenic
Neuronal Plasticity
Social Isolation
Synapses

Semantics

Type Source Name
disease MESH coronavirus disease 2019
disease MESH causes
disease MESH cognitive impairments
disease MESH mental disorders
disease IDO production
disease IDO intervention
disease MESH dementia
disease MESH memory loss
disease MESH senile plaques
pathway REACTOME Apoptosis
disease MESH Neurological Disorders
disease MESH Emergency
drug DRUGBANK Coenzyme M
drug DRUGBANK Water
drug DRUGBANK Isoflurane
drug DRUGBANK Ethanol
disease MESH shock
drug DRUGBANK Sucrose
disease MESH anhedonia
disease MESH anxiety
disease MESH posture
drug DRUGBANK Ketamine
drug DRUGBANK Trypsin
pathway REACTOME Digestion
drug DRUGBANK Aspartame
drug DRUGBANK L-Lysine
drug DRUGBANK Streptomycin
drug DRUGBANK Potassium Chloride
drug DRUGBANK Magnesium sulfate
drug DRUGBANK Sodium bicarbonate
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Sodium lauryl sulfate
disease IDO reagent
drug DRUGBANK Glycerin
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Tromethamine
drug DRUGBANK Formic Acid
disease IDO assay
drug DRUGBANK Mercuric chloride
drug DRUGBANK Gelatin
disease MESH depression
drug DRUGBANK Proline
disease MESH pus
pathway REACTOME Translation
disease IDO process
disease MESH tic
disease MESH weaning
disease MESH loneliness
drug DRUGBANK Corticosterone
disease MESH lifestyle
disease MESH Oxidative Stress
disease MESH Tauopathies
drug DRUGBANK Methylergometrine
drug DRUGBANK Histidine
disease MESH Alzheimer Disease
pathway KEGG Alzheimer disease
disease MESH hearing impairment
disease MESH frailty
disease MESH Marital status
drug DRUGBANK Trestolone
pathway REACTOME Autophagy
pathway REACTOME Reproduction
disease MESH Disease Models Animal

Original Article

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