Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice
Author
Bunner, Wyatt; Wang, Jie; Cohen, Sarah; Bashtovyy, Denys; Perry, Rachel; Shookster, Daniel; Landry, Taylor; Harris, Elizabeth M.; Stackman, Robert; Tran, Tuan D.; Yasuda, Ryohei; Szatmari, Erzsebet M.
Abstract
A central question in the field of aging research is to identify the cellular and molecular basis of neuroresilience. One potential candidate is the small GTPase, Rab10. Here, we used Rab101/ mice to investigate the molecular mecha-nisms underlying Rab10-mediated neuroresilience. Brain expression analysis of 880 genes involved in neurodegener-ation showed that Rab101/ mice have increased activation of pathways associated with neuronal metabolism, structural integrity, neurotransmission, and neuroplasticity compared with their Rab101/1 littermates. Lower activation was observed for pathways involved in neuroinflammation and aging. We identified and validated several differentially expressed genes (DEGs), including Stx2, Stx1b, Vegfa, and Lrrc25 (downregulated) and Prkaa2, Syt4, and Grin2d (upregulated). Behavioral testing showed that Rab101/ mice perform better in a hippocampal-dependent spatial task (object in place test), while their performance in a classical conditioning task (trace eyeblink classical condition-ing, TECC) was significantly impaired. Therefore, our findings indicate that Rab10 differentially controls the brain cir-cuitry of hippocampal-dependent spatial memory and higher-order behavior that requires intact cortex-hippocampal circuitry. Transcriptome and biochemical characterization of these mice suggest that glutamate ionotropic receptor NMDA type subunit 2D (GRIN2D or GluN2D) is affected by Rab10 signaling. Further work is needed to evaluate whether GRIN2D mediates the behavioral phenotypes of the Rab101/ mice. We conclude that Rab101/ mice de-scribed here can be a valuable tool to study the mechanisms of resilience in Alzheimer’s disease (AD) model mice and to identify novel therapeutical targets to prevent cognitive decline associated with normal and pathologic aging.
Description
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Subject
Date
2023-05-08
Citation:
APA:
Bunner, Wyatt, & Wang, Jie, & Cohen, Sarah, & Bashtovyy, Denys, & Perry, Rachel, & Shookster, Daniel, & Landry, Taylor, & Harris, Elizabeth M., & Stackman, Robert, & Tran, Tuan D., & Yasuda, Ryohei, & Szatmari, Erzsebet M.. (May 2023).
Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/13105
MLA:
Bunner, Wyatt, and Wang, Jie, and Cohen, Sarah, and Bashtovyy, Denys, and Perry, Rachel, and Shookster, Daniel, and Landry, Taylor, and Harris, Elizabeth M., and Stackman, Robert, and Tran, Tuan D., and Yasuda, Ryohei, and Szatmari, Erzsebet M..
"Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice". .
. (),
May 2023.
April 29, 2024.
http://hdl.handle.net/10342/13105.
Chicago:
Bunner, Wyatt and Wang, Jie and Cohen, Sarah and Bashtovyy, Denys and Perry, Rachel and Shookster, Daniel and Landry, Taylor and Harris, Elizabeth M. and Stackman, Robert and Tran, Tuan D. and Yasuda, Ryohei and Szatmari, Erzsebet M.,
"Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice," , no.
(May 2023),
http://hdl.handle.net/10342/13105 (accessed
April 29, 2024).
AMA:
Bunner, Wyatt, Wang, Jie, Cohen, Sarah, Bashtovyy, Denys, Perry, Rachel, Shookster, Daniel, Landry, Taylor, Harris, Elizabeth M., Stackman, Robert, Tran, Tuan D., Yasuda, Ryohei, Szatmari, Erzsebet M..
Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice. .
May 2023;
():
.
http://hdl.handle.net/10342/13105. Accessed
April 29, 2024.
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