Dataset Information

Rod pathway and cone pathway retinal dysfunction in the 5xFAD mouse model of Alzheimer's disease.

ABSTRACT: To characterize rod- and cone-pathway function in the 5xFAD mouse model of Alzheimer's disease (AD) using the full-field electroretinogram (ERG). Dark-adapted (DA; rod-pathway) and light-adapted (LA; cone-pathway) ERGs were recorded from three-month-old 5xFAD and wild type (WT) mice. ERGs were elicited by achromatic flashes (0.01-25 cd-s-m^-²). Amplitude and implicit time (IT) of the a-wave, b-wave, and oscillatory potentials (OPs) were calculated according to convention. In addition, the amplitude and IT of the photopic negative response (PhNR) were measured from the LA recordings. Amplitude and IT differences between the 5xFAD and WT groups were evaluated using quantile regression models. Under DA conditions, there were significant differences between the 5xFAD and WT groups in post-receptor function, whereas photoreceptor function did not differ significantly. Specifically, the DA a-wave amplitude did not differ between groups (p?=?0.87), whereas the b-wave amplitude was reduced in the 5xFAD mice (p?=?0.003). There were significant OP (p?

SUBMITTER: McAnany JJ

PROVIDER: S-EPMC7921657 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Rod pathway and cone pathway retinal dysfunction in the 5xFAD mouse model of Alzheimer's disease.

McAnany J Jason JJ Matei Nathanael N Chen Yi-Fan YF Liu Karen K Park Jason C JC Shahidi Mahnaz M

Scientific reports 20210301 1

To characterize rod- and cone-pathway function in the 5xFAD mouse model of Alzheimer's disease (AD) using the full-field electroretinogram (ERG). Dark-adapted (DA; rod-pathway) and light-adapted (LA; cone-pathway) ERGs were recorded from three-month-old 5xFAD and wild type (WT) mice. ERGs were elicited by achromatic flashes (0.01-25 cd-s-m<sup>-</sup><sup>2</sup>). Amplitude and implicit time (IT) of the a-wave, b-wave, and oscillatory potentials (OPs) were calculated according to convention. In ...[more]

PMID: 33649406

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Project description:There is an urgent need to improve the translational validity of Alzheimer's disease (AD) mouse models. Introducing genetic background diversity in AD mouse models has been proposed as a way to increase validity and enable the discovery of previously uncharacterized genetic contributions to AD susceptibility or resilience. However, the extent to which genetic background influences the mouse brain proteome and its perturbation in AD mouse models is unknown. In this study, we crossed the 5XFAD AD mouse model on a C57BL/6J (B6) inbred background with the DBA/2J (D2) inbred background and analyzed the effects of genetic background variation on the brain proteome in F1 progeny. Both genetic background and 5XFAD transgene insertion strongly affected protein variance in the hippocampus and cortex (n = 3,368 proteins). Protein co-expression network analysis identified 16 modules of highly co-expressed proteins common across the hippocampus and cortex in 5XFAD and non-transgenic mice. Among the modules strongly influenced by genetic background were those related to small molecule metabolism and ion transport. Modules strongly influenced by the 5XFAD transgene were related to lysosome/stress responses and neuronal synapse/signaling. The modules with the strongest relationship to human disease-neuronal synapse/signaling and lysosome/stress response-were not significantly influenced by genetic background. However, other modules in 5XFAD that were related to human disease, such as GABA synaptic signaling and mitochondrial membrane modules, were influenced by genetic background. Most disease-related modules were more strongly correlated with AD genotype in the hippocampus compared with the cortex. Our findings suggest that the genetic diversity introduced by crossing B6 and D2 inbred backgrounds influences proteomic changes related to disease in the 5XFAD model, and that proteomic analysis of other genetic backgrounds in transgenic and knock-in AD mouse models is warranted to capture the full range of molecular heterogeneity in genetically diverse models of AD.

Dataset Information

Rod pathway and cone pathway retinal dysfunction in the 5xFAD mouse model of Alzheimer's disease.

Publications

Rod pathway and cone pathway retinal dysfunction in the 5xFAD mouse model of Alzheimer's disease.

Similar Datasets

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