Angiotensin II differentially affects hippocampal glial inflammatory markers in young adult male and female mice

Milner, Teresa A.; Chen, Ryan X.; Welington, Diedreanna; Rubin, Batsheva R.; Contoreggi, Natalina H.; Johnson, Megan A.; Mazid, Sanoara; Marques-Lopes, José; Marongiu, Roberta; Glass, Michael R.

doi:10.1101/lm.053507.121

Cited by 3 publications

(1 citation statement)

References 80 publications

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“…The density of the astrocytic marker GFAP was examined in CA1, CA3, DG and subicular subregions within rostral and caudal hippocampus (Figures 3A,B) of oil and VCD-treated SWDI and WT mice. Consistent with our prior studies in female mouse brain (Milner et al, 2022), GFAP-labeled cells were found throughout the CA1, CA3 and DG (Figure 3). Representative micrographs of GFAP-labeling are shown for rostral CA1 (Figures 3C-F), caudal CA1/subiculum (Figures 3H-K) and the dentate gyrus (Figures 3M,N).…”

Section: Peri-aof Is Associated With Increased Levels Of Reactive Ast...supporting

confidence: 92%

Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy

Platholi,

Marongiu,

Park

et al. 2023

Front. Aging Neurosci.

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Dementia is often characterized by age-dependent cerebrovascular pathology, neuroinflammation, and cognitive deficits with notable sex differences in risk, disease onset, progression and severity. Women bear a disproportionate burden of dementia, and the onset of menopause (i.e., perimenopause) may be a critical period conferring increased susceptibility. However, the contribution of early ovarian decline to the neuroinflammatory processes associated with cerebrovascular dementia risks, particularly at the initial stages of pathology that may be more amenable to proactive intervention, is unknown. To better understand the influence of early ovarian failure on dementia-associated neuroinflammation we developed a model of perimenopausal cerebral amyloid angiopathy (CAA), an important contributor to dementia. For this, accelerated ovarian failure (AOF) was induced by 4-vinylcyclohexene diepoxide (VCD) treatment to isolate early-stage ovarian failure comparable to human perimenopause (termed “peri-AOF”) in transgenic SWDI mice expressing human vasculotropic mutant amyloid beta (Aβ) precursor protein, that were also tested at an early stage of amyloidosis. We found that peri-AOF SWDI mice showed increased astrocyte activation accompanied by elevated Aβ in select regions of the hippocampus, a brain system involved in learning and memory that is severely impacted during dementia. However, although SWDI mice showed signs of increased hippocampal microglial activation and impaired cognitive function, this was not further affected by peri-AOF. In sum, these results suggest that elevated dysfunction of key elements of the neurovascular unit in select hippocampal regions characterizes the brain pathology of mice at early stages of both CAA and AOF. However, neurovascular unit pathology may not yet have passed a threshold that leads to further behavioral compromise at these early periods of cerebral amyloidosis and ovarian failure. These results are consistent with the hypothesis that the hormonal dysregulation associated with perimenopause onset represents a stage of emerging vulnerability to dementia-associated neuropathology, thus providing a selective window of opportunity for therapeutic intervention prior to the development of advanced pathology that has proven difficult to repair or reverse.

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Section: Peri-aof Is Associated With Increased Levels Of Reactive Ast...supporting

confidence: 92%

Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy

Platholi,

Marongiu,

Park

et al. 2023

Front. Aging Neurosci.

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Peripheral to brain and hippocampus crosstalk induced by exercise mediates cognitive and structural hippocampal adaptations

Blume,

Royes

2024

Life Sciences

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Estrogen receptor beta activity contributes to both tumor necrosis factor alpha expression in the hypothalamic paraventricular nucleus and the resistance to hypertension following angiotensin II in female mice

Woods

Contoreggi²,

Johnson³

et al. 2022

Neurochemistry International

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Angiotensin II differentially affects hippocampal glial inflammatory markers in young adult male and female mice

Cited by 3 publications

References 80 publications

Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy

Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy

Peripheral to brain and hippocampus crosstalk induced by exercise mediates cognitive and structural hippocampal adaptations

Estrogen receptor beta activity contributes to both tumor necrosis factor alpha expression in the hypothalamic paraventricular nucleus and the resistance to hypertension following angiotensin II in female mice

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