ApoE4 Exacerbates Hippocampal Pathology Following Acute Brain Penetration Injury in Female Mice

Ben-Moshe, Hila; Luz, Ishai; Liraz, Ori; Boehm-Cagan, Anat; Salomon-Zimri, Shiran; Michaelson, Daniel M.

doi:10.1007/s12031-019-01397-7

Cited by 8 publications

(4 citation statements)

References 70 publications

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“…LPS treatment of primary APOE4 microglial cultures led to more extensive neuron damage compared to APOE3 microglia [134], with similar experiments entailing in vitro exposure to LPS inducing significantly elevated pro-inflammatory cytokine production in APOE4 microglia [135]. The induction of acute brain injury from needle penetration resulted in greater inflammatory responses as measured by reactive astrocytes and microglia in APOE4 mice [136]. Control APOE4 mice had a lower dendritic spine density [137,138], likely a result of increased inflammation, as this phenotype was alleviated with nonsteroidal anti-inflammatory drug treatment [139].…”

Section: Apoe Genotype and Neuroinflammationmentioning

confidence: 87%

Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Fernandez

Varma

Flowers

et al. 2020

Cancers

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Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (APOE), which is also the strongest genetic risk factor for Alzheimer’s disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of APOE4 on CRCI takes on great significance. This review outlines the main areas where APOE genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the APOE genotype could help in developing personalized cancer treatment regimens.

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Section: Apoe Genotype and Neuroinflammationmentioning

confidence: 87%

Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Fernandez

Varma

Flowers

et al. 2020

Cancers

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“…In mouse models of amyloid, APOE4 is associated with increased Aβ levels and earlier deposition when compared with APOE3 ( Tai et al, 2013 ; Tai et al, 2017 ; Youmans et al, 2012a). APOE isoforms also modulate glial activation in response to several types of damage, including amyloid, lipopolysaccharide, and acute brain injuries ( Rodriguez et al, 2014 ; Zhu et al, 2012 ; Kloske and Wilcock, 2020 ; Ben-Moshe et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE

Biran

Galvano

et al. 2022

Neurobiology of Disease

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“…Most of these studies have used transgenic mice that overexpress human apoE in an endogenous gene-deleted background [ 7 , 8 ]. In recent years, a physiological model of apoE knock-in (KI) mice [ 9 ] has been studied [ 10 - 13 ]. These mice showed increased inflammation with neurodegeneration after focal penetrating injury [ 12 ] and blast injury [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, a physiological model of apoE knock-in (KI) mice [ 9 ] has been studied [ 10 - 13 ]. These mice showed increased inflammation with neurodegeneration after focal penetrating injury [ 12 ] and blast injury [ 13 ]. However, in response to single cortical impact, the differential effects of apoE4 cannot be clearly validated [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Region-Specific Differences in the Apoe4-dependent Response to Focal Brain Injury

et al. 2021

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Apolipoprotein E (apoE) plays a role in various physiological functions including lipid transport, synaptic plasticity, and immune modulation. Epidemiological studies suggest that the apoE4 allele increases the risk of post-traumatic sequelae. This study was performed to investigate regionspecific effects of the apoE4 isoform on post-traumatic neurodegeneration. Two focal brain injuries were introduced separately in the motor cortex and hippocampus of apoE4 knock-in, apoE3 knock-in, apoE knockout, and wild-type (WT) mice. Western blotting showed that the expression levels of pre-synaptic and post-synaptic markers at the recovery stage were lower in the hippocampal injury core in apoE4 mice, compared with apoE3 and WT mice. Fast glial activation (determined by immunohistochemistry with glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and cluster of differentiation 45 antibodies) was characteristic of apoE4 mice with hippocampal injury penumbra. apoE4-specific changes were not observed after cortical injury. The intensity of microglial activation in the hippocampus was inversely correlated with the volume of injury reduction on sequential magnetic resonance imaging examinations, when validated using matched samples. These findings indicate that the effects of the interaction between apoE4 and focal brain damage are specific to the hippocampus. Manipulation of inflammatory cell responses could be beneficial for reducing post-traumatic hippocampal neurodegeneration in apoE4 carriers.

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ApoE4 Exacerbates Hippocampal Pathology Following Acute Brain Penetration Injury in Female Mice

Cited by 8 publications

References 70 publications

Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE

Region-Specific Differences in the Apoe4-dependent Response to Focal Brain Injury

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