Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer's disease.

ABSTRACT: Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty and stress, and also regulates neuroinflammation. We previously demonstrated behavioral and immunomodulatory effects of beta-adrenergic pharmacology in mouse models of Alzheimer's disease (AD). The current studies were designed to block noradrenergic signaling in 5XFAD mice through 1 ) chemogenetic inhibition of the locus coeruleus (LC), 2) pharmacologic blocking of β-adrenergic receptors, and 3) conditional deletion of β1- or β2-adrenergic receptors (adrb1 or adrb2) in microglia. First, brain-wide AD pathology was mapped in 3D by imaging immunolabeled, cleared 5XFAD brains to assess the overlap between Aβ pathology, reactive microglia, and the loss of tyrosine hydroxylase (T

SUBMITTER: Evans AK 

PROVIDER: S-EPMC11581111 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature