Behavioral Deficits in Mice with Postnatal Disruption of Ndel1 in Forebrain Excitatory Neurons: Implications for Epilepsy and Neuropsychiatric Disorders

Author:

Gavrilovici Cezar1,Jiang Yulan2,Kiroski Ivana2,Sterley Toni-Lee3,Vandal Milene2,Bains Jaideep3,Park Sang Ki4,Rho Jong M1,Teskey G Campbell5,Nguyen Minh Dang2ORCID

Affiliation:

1. Departments of Neurosciences & Pediatrics, University of California San Diego, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA

2. Departments of Clinical Neurosciences, Cell Biology and Anatomy, and Biochemistry and Molecular Biology, Hotchkiss Brain Institute, Calgary, AB T2N 4N1, Canada

3. Departments of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada

4. Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea

5. Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Calgary, AB T2N 4N1, Canada

Abstract

Abstract Dysfunction of nuclear distribution element-like 1 (Ndel1) is associated with schizophrenia, a neuropsychiatric disorder characterized by cognitive impairment and with seizures as comorbidity. The levels of Ndel1 are also altered in human and models with epilepsy, a chronic condition whose hallmark feature is the occurrence of spontaneous recurrent seizures and is typically associated with comorbid conditions including learning and memory deficits, anxiety, and depression. In this study, we analyzed the behaviors of mice postnatally deficient for Ndel1 in forebrain excitatory neurons (Ndel1 CKO) that exhibit spatial learning and memory deficits, seizures, and shortened lifespan. Ndel1 CKO mice underperformed in species-specific tasks, that is, the nest building, open field, Y maze, forced swim, and dry cylinder tasks. We surveyed the expression and/or activity of a dozen molecules related to Ndel1 functions and found changes that may contribute to the abnormal behaviors. Finally, we tested the impact of Reelin glycoprotein that shows protective effects in the hippocampus of Ndel1 CKO, on the performance of the mutant animals in the nest building task. Our study highlights the importance of Ndel1 in the manifestation of species-specific animal behaviors that may be relevant to our understanding of the clinical conditions shared between neuropsychiatric disorders and epilepsy.

Funder

KNRF

Brain Research Program

the Alberta Children’s Hospital Research Institute

Alberta Innovates Health Solutions

Canadian Institutes of Health Research

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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