Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer's disease. DOI Creative Commons
Andrew K. Evans,

Heui Hye Park,

Claire E. Woods

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty stress, also regulates neuroinflammation. We previously demonstrated behavioral immunomodulatory effects of beta-adrenergic pharmacology in mouse models Alzheimer's disease (AD). The current studies were designed block noradrenergic signaling 5XFAD mice through 1) chemogenetic inhibition the locus coeruleus (LC), 2)pharmacologic blocking β-adrenergic receptors, 3) conditional deletion β1- or β2-adrenergic receptors (adrb1 adrb2) microglia. First, brain-wide AD pathology was mapped 3D by imaging immunolabeled, cleared brains assess overlap between Aβ pathology, reactive microglia, loss tyrosine hydroxylase (TH) expression catecholaminergic system. To examine inhibiting LC NE system model, inhibitory (Gi) DREADD expressed specifically neurons. neurons chronically inhibited subcutaneous pump administration agonist clozapine-N-oxide (CNO). Plasma collected for assessment neuroinflammation pathology. A separate cohort dosed with antagonist propranolol vehicle evaluated behavior, as well post-mortem Finally, we used conditional either adrb1 adrb2 microglia mediated signaling. Using iDISCO, light sheet fluorescence microscopy, novel analyses, detected widespread microgliosis amyloid along modest TH downregulation fibers across multiple brain regions, contrast spatially limited observed Both adrenergic pharmacological potentiated without altering beta Conditional did not affect attenuated inflammation females but had no effect males. Overall, these data support previous observations demonstrating pathophysiology disorders suggest that on cell types other than such astrocytes, may predominantly mediate disease-modifying agonists brain.

Language: Английский

Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer’s disease DOI Creative Commons
Andrew K. Evans,

Heui Hye Park,

Claire E. Woods

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Dec. 18, 2024

Abstract Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty stress, it also regulates neuroinflammation. We previously demonstrated behavioral immunomodulatory effects of beta-adrenergic pharmacology in mouse models Alzheimer’s disease (AD). The current studies were designed block noradrenergic signaling 5XFAD mice through ( 1 ) chemogenetic inhibition the locus coeruleus (LC), 2 pharmacologic blocking β-adrenergic receptors, 3 conditional deletion β1- or β2-adrenergic receptors (adrb1 adrb2) microglia. First, brain-wide AD pathology was mapped 3D by imaging immunolabeled, cleared brains assess overlap between amyloid beta (Aβ) pathology, reactive microglia, loss tyrosine hydroxylase (TH) expression catecholaminergic system. To examine inhibiting LC NE system model, inhibitory (Gi) DREADD expressed specifically neurons. neurons chronically inhibited subcutaneous pump administration agonist clozapine-N-oxide (CNO). Plasma collected for assessment neuroinflammation pathology. A separate cohort dosed with antagonist propranolol vehicle evaluated behavior, as well post-mortem Finally, we used either adrb1 adrb2 microglia mediated signaling. Using iDISCO+, light sheet fluorescence microscopy, novel analyses, detected widespread microgliosis Aβ along modest TH downregulation fibers across multiple brain regions, contrast spatially limited observed Both adrenergic pharmacological potentiated without altering Conditional did not affect attenuated inflammation females but had no effect males. Overall, these data support previous observations demonstrating pathophysiology disorders suggest that on cell types other than such astrocytes, may mediate some disease-modifying agonists brain.

Language: Английский

Citations

1
Brain image data processing using collaborative data workflows on Texera DOI Creative Commons

Yunyan Ding,

Yicong Huang,

Pan Gao

et al.

Frontiers in Neural Circuits, Journal Year: 2024, Volume and Issue: 18

Published: July 10, 2024

In the realm of neuroscience, mapping three-dimensional (3D) neural circuitry and architecture brain is important for advancing our understanding circuit organization function. This study presents a novel pipeline that transforms mouse samples into detailed 3D models using collaborative data analytics platform called "Texera." The user-friendly Texera allows effective interdisciplinary collaboration between team members in computer vision, processing. Our utilizes tile images from serial two-photon tomography/TissueCyte system, then stitches section images, constructs whole-brain image datasets. resulting supports downstream analyses, including registration, atlas-based segmentation, cell counting, high-resolution volumetric visualization. Using this platform, we implemented specialized optimization methods obtained significant performance enhancement workflow operations. We expect neuroscience community can adopt approach large-scale image-based processing analysis.

Language: Английский

Citations

0
Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer's disease. DOI Creative Commons
Andrew K. Evans,

Heui Hye Park,

Claire E. Woods

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty stress, also regulates neuroinflammation. We previously demonstrated behavioral immunomodulatory effects of beta-adrenergic pharmacology in mouse models Alzheimer's disease (AD). The current studies were designed block noradrenergic signaling 5XFAD mice through 1) chemogenetic inhibition the locus coeruleus (LC), 2)pharmacologic blocking β-adrenergic receptors, 3) conditional deletion β1- or β2-adrenergic receptors (adrb1 adrb2) microglia. First, brain-wide AD pathology was mapped 3D by imaging immunolabeled, cleared brains assess overlap between Aβ pathology, reactive microglia, loss tyrosine hydroxylase (TH) expression catecholaminergic system. To examine inhibiting LC NE system model, inhibitory (Gi) DREADD expressed specifically neurons. neurons chronically inhibited subcutaneous pump administration agonist clozapine-N-oxide (CNO). Plasma collected for assessment neuroinflammation pathology. A separate cohort dosed with antagonist propranolol vehicle evaluated behavior, as well post-mortem Finally, we used conditional either adrb1 adrb2 microglia mediated signaling. Using iDISCO, light sheet fluorescence microscopy, novel analyses, detected widespread microgliosis amyloid along modest TH downregulation fibers across multiple brain regions, contrast spatially limited observed Both adrenergic pharmacological potentiated without altering beta Conditional did not affect attenuated inflammation females but had no effect males. Overall, these data support previous observations demonstrating pathophysiology disorders suggest that on cell types other than such astrocytes, may predominantly mediate disease-modifying agonists brain.

Language: Английский

Citations

0