Sex differences in a murine model of Cerebral Amyloid Angiopathy

Maniskas, Michael E; Mack, Alexis F.; Morales-Scheihing, Diego; Finger, Carson; Zhu, Liang; Paulter, Robia; Urayama, Akihiko; McCullough, Louise D.; Manwani, Bharti

doi:10.1016/j.bbih.2021.100260

Cited by 12 publications

(10 citation statements)

References 66 publications

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“…However, the possibility of concomitant CAA in our patients cannot be completely ruled out. In animal models of CAA, female mice had a significantly higher burden of CMBs than males ( 30 ). Further research and data collection, including those on amyloid positivity, are needed to identify sex differences in the progression of CMBs based on their underlying pathology.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease

et al. 2022

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Background and purposeSex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs.MethodsThe CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women.ResultsA total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0–7) vs. 2 (0–7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0–2) vs. 0 (0–1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs].ConclusionThe progression of CMB over 2 years was significantly greater in women than in men.

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Section: Discussionmentioning

confidence: 99%

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease

et al. 2022

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“…The Barnes maze test [ 83 , 84 ] and fear conditioning test [ 85 , 86 ] with modifications were used to assess spatial and associative learning and memory in mice, respectively. Briefly, the Barnes maze test was performed using an elevated circular platform that had 20 holes evenly spaced.…”

Section: Methodsmentioning

confidence: 99%

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement

Tashiro

Ozaki

Bautista-Garrido

et al. 2023

IJMS

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Aging drives cognitive decline, and mitochondrial dysfunction is a hallmark of age-induced neurodegeneration. Recently, we demonstrated that astrocytes secrete functional mitochondria (Mt), which help adjacent cells to resist damage and promote repair after neurological injuries. However, the relationship between age-dependent changes in astrocytic Mt function and cognitive decline remains poorly understood. Here, we established that aged astrocytes secret less functional Mt compared to young astrocytes. We found the aging factor C-C motif chemokine 11 (CCL11) is elevated in the hippocampus of aged mice, and that its level is reduced upon systemic administration of young Mt, in vivo. Aged mice receiving young Mt, but not aged Mt improved cognitive function and hippocampal integrity. Using a CCL11-induced aging-like model in vitro, we found that astrocytic Mt protect hippocampal neurons and enhance a regenerative environment through upregulating synaptogenesis-related gene expression and anti-oxidants that were suppressed by CCL11. Moreover, the inhibition of CCL11-specific receptor C-C chemokine receptor 3 (CCR3) boosted the expression of synaptogenesis-related genes in the cultured hippocampal neurons and restored the neurite outgrowth. This study suggests that young astrocytic Mt can preserve cognitive function in the CCL11-mediated aging brain by promoting neuronal survival and neuroplasticity in the hippocampus.

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“…Beckmann et al showed microhemorrhages in β-secretase inhibitor-treated APP23 mice by using T 2 *-weighted imaging [ 165 ]. A recent study by Maniskas et al demonstrated a gender difference in the number of cerebral microbleeds by using a T 2 * sequence in Tg-SwDI mice (with a higher load of microbleeds in female mice) [ 166 ]. SWI and QSM have been performed in arcAβ, APP/PS1, and CVN-AD mice at 9.4 T [ 81 , 112 , 167 , 168 , 169 ].…”

Section: Cerebrovascular Imagingmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

2021

IJMS

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Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.

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Sex differences in a murine model of Cerebral Amyloid Angiopathy

Cited by 12 publications

References 66 publications

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

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