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. 2023 Mar 2;13(3):686.
doi: 10.3390/life13030686.

Sex and Age-Dependent Olfactory Memory Dysfunction in ADHD Model Mice

Jae-Sang Sim  1 , Won-Seok Lee  1 , Bo-Eun Yoon  1
Affiliations

Sex and Age-Dependent Olfactory Memory Dysfunction in ADHD Model Mice

Jae-Sang Sim et al. Life (Basel). .

Abstract

ADHD is a typical neurodevelopmental disorder with a high prevalence rate. NSCs in the subventricular zone (SVZ) are closely related to neurodevelopmental disorder and can affect olfactory function by neurogenesis and migratory route. Although olfactory dysfunction is one of the symptoms of ADHD, the relevance of cells in the olfactory bulb derived from NSCs has not been studied. Therefore, we investigated olfactory memory and NSCs in Git1-deficient mice, under the ADHD model. Interestingly, only adult male G protein-coupled receptor kinase-interacting protein-1 (GIT1)-deficient (+/-, HE) mice showed impaired olfactory memory, suggesting sex and age dependence. We performed adult NSCs culture from the SVZ and observed distinct cell population in both sex and genotype. Taken together, our study suggests that the altered differentiation of NSCs in GIT1+/- mice can contribute to olfactory dysfunction in ADHD.

Keywords: ADHD; GIT1; neural stem cell; olfactory memory.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Scheme of behavioral experiment of olfactory memory test. Baseline time and sniff time was measured at training phase and recall phase, respectively. The arrow below shows the timeline for the behavior test and selegiline administration. (b,d) are baseline time of sniffing in training phase for adolescent (b) males (left) and females (right), and adult (d) males (left) and females (right). (c,e–g) Percentage of sniffing time in recall phase about training phase depending on interval. The graphs indicated the percentage of sniffing times of adolescent males (c) and females (d), and adult males (f) and females (g). * p < 0.1, ** p < 0.01, *** p < 0.001, “ns”—non-significant.
Figure 2
Figure 2
Doublecortin intensity of immature neuron in rostral migratory stream. (a,c) Representative images of DAB staining for doublecortin in rostral migratory stream from adult GIT1 male and female mice. (b,d) Relative optical density of doublecortin in rostral migratory stream from adult GIT1 male and female mice. Optical density was analyzed in region of interest (ROI; white dashed line). ** p < 0.01, “ns”—non-significant.
Figure 3
Figure 3
Differentiation of subventricular zone neural stem cells in adult GIT1 mice. (a,b) Representative images of immunocytochemistry in differentiation of neural stem cells from adult GIT1 male and female mice (left-WT, right-HE/blue-DAPI, green-MAP2, magenta-S100β). (c,d) Percentage of differentiation from neural stem cell to neuron (left) and astrocyte (right), scale bar = 50 μm. *** p < 0.001, “ns”—non-significant.
See this image and copyright information in PMC

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