Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice

Batool, Shadab; Akhter, Basma; Zaidi, Jawwad; Visser, Frank; Petrie, Gavin; Hill, Matthew; Syed, Naweed I.

doi:10.3390/cells10123286

Open AccessArticle

Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice

by

Shadab Batool

^1,2,

Basma Akhter

¹,

Jawwad Zaidi

³,

Frank Visser

¹,

Gavin Petrie

^1,2,

Matthew Hill

¹ and

Naweed I. Syed

^4,*

¹

Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada

²

Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada

³

Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada

⁴

Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada

^*

Author to whom correspondence should be addressed.

Cells 2021, 10(12), 3286; https://doi.org/10.3390/cells10123286

Submission received: 29 October 2021 / Revised: 14 November 2021 / Accepted: 17 November 2021 / Published: 24 November 2021

(This article belongs to the Collection Feature Papers in 'Cells of the Nervous System' Section)

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Abstract

The perturbation of nicotinic cholinergic receptors is thought to underlie many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s and schizophrenia. We previously identified that the tumor suppressor gene, MEN1, regulates both the expression and synaptic targeting of α7 nAChRs in the mouse hippocampal neurons in vitro. Here we sought to determine whether the α7 nAChRs gene expression reciprocally regulates the expression of menin, the protein encoded by the MEN1 gene, and if this interplay impacts learning and memory. We demonstrate here that α7 nAChRs knockdown (KD) both in in vitro and in vivo, initially upregulated and then subsequently downregulated menin expression. Exogenous expression of menin using an AAV transduction approach rescued α7 nAChRs KD mediated functional and behavioral deficits specifically in hippocampal (CA1) neurons. These effects involved the modulation of the α7 nAChR subunit expression and functional clustering at the synaptic sites. Our data thus demonstrates a novel and important interplay between the MEN1 gene and the α7 nAChRs in regulating hippocampal-dependent learning and memory.

Keywords: learning and memory; nicotinic cholinergic receptors; menin; synaptogenesis; extracellular activity; brain connectivity

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MDPI and ACS Style

Batool, S.; Akhter, B.; Zaidi, J.; Visser, F.; Petrie, G.; Hill, M.; Syed, N.I. Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice. Cells 2021, 10, 3286. https://doi.org/10.3390/cells10123286

AMA Style

Batool S, Akhter B, Zaidi J, Visser F, Petrie G, Hill M, Syed NI. Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice. Cells. 2021; 10(12):3286. https://doi.org/10.3390/cells10123286

Chicago/Turabian Style

Batool, Shadab, Basma Akhter, Jawwad Zaidi, Frank Visser, Gavin Petrie, Matthew Hill, and Naweed I. Syed. 2021. "Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice" Cells 10, no. 12: 3286. https://doi.org/10.3390/cells10123286

APA Style

Batool, S., Akhter, B., Zaidi, J., Visser, F., Petrie, G., Hill, M., & Syed, N. I. (2021). Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice. Cells, 10(12), 3286. https://doi.org/10.3390/cells10123286

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Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice

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