Archival ReportSex Differences in the Role of CNIH3 on Spatial Memory and Synaptic Plasticity
Section snippets
Animals
Procedures were approved by the Institutional Animal Care and Use Committee at Washington University in St. Louis. Adult (8–16 weeks) male and female C57BL/6 wild-type (WT) (Cnih3+/+), Cnih3tm1a(KOMP)Wtsi, and Cnih3 knockout (KO) (Cnih3−/−) mice were kept in climate-controlled facilities with a 12-hour light/dark cycle and ad libitum access to food and water.
β-Galactosidase Staining
To visualize the anatomical expression of the Cnih3tm1a(KOMP)Wtsi gene in the brain, we stained the brains of homozygous mutant mice for
LacZ-Tagged Cnih3 Prominently Expressed in the Hippocampus
To identify anatomical expression of Cnih3 in the brain, we used a β-galactosidase staining assay to visualize the lacZ cassette contained within the Cnih3tm1a(KOMP)Wtsi gene of Cnih3tm1a(KOMP)Wtsi mice (51) (Figure 1A). No lacZ staining was observed in WT lacZ− brains (Figure 1B). In lacZ+ brains, lacZ reporter expression was strongest in the prefrontal cortex, hypothalamus, cortical regions, amygdala, and hippocampus (Figure 1C–E, males and females) (19). Within the hippocampus, lacZ reporter
Discussion
Learning and memory play a pivotal role in animal behavior, and dysregulation of the memory mechanisms are found in a wide array of psychiatric disorders. In this study, overexpression of Cnih3 in the dHPC improved short-term spatial memory only in female mice, whereas short-term spatial memory was attenuated only in female Cnih3−/− mice. Impairments in spatial memory of female Cnih3−/− mice were particularly apparent during metestrus, a stage characterized by low circulating levels of
Acknowledgments and Disclosures
This work was funded by the National Institutes of Health (Grant Nos. DA041781, DA042581, DA042499, and DA045463 [to JAM]; Grant No. DA041883 [to JAM, ECN, and JDD]; Grant Nos. DA046436 and DA042620 [to ECN]; Grant No. I01BX005204 [to TTK]; and Grant No. GM008151 [to Washington University and HEF]), the BrightFocus Foundation (Grant No. A2017084S [to TTK]), the Brain Research Foundation (Grant No. BRFSG-2017-05 [to TTK]), and the McDonnell Center for Cellular and Molecular Neurobiology (to TTK).
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