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 it 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 amyloid beta (Aβ) pathology, reactive microglia, and the loss of tyrosine hydroxylase (TH)

SUBMITTER: Evans AK 

PROVIDER: S-EPMC11657531 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature