PMID- 34943798
OWN - NLM
STAT- MEDLINE
DCOM- 20220120
LR  - 20240226
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 10
IP  - 12
DP  - 2021 Nov 24
TI  - Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in 
      CA1-Specific alpha7 nAChRs KD Mice.
LID - 10.3390/cells10123286 [doi]
LID - 3286
AB  - 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 alpha7 nAChRs in the mouse 
      hippocampal neurons in vitro. Here we sought to determine whether the alpha7 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 alpha7 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 alpha7 
      nAChRs KD mediated functional and behavioral deficits specifically in hippocampal 
      (CA1) neurons. These effects involved the modulation of the alpha7 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 alpha7 
      nAChRs in regulating hippocampal-dependent learning and memory.
FAU - Batool, Shadab
AU  - Batool S
AD  - Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
AD  - Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Akhter, Basma
AU  - Akhter B
AD  - Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Zaidi, Jawwad
AU  - Zaidi J
AD  - Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Visser, Frank
AU  - Visser F
AD  - Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Petrie, Gavin
AU  - Petrie G
AD  - Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
AD  - Department of Neuroscience, University of Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Hill, Matthew
AU  - Hill M
AD  - Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Syed, Naweed I
AU  - Syed NI
AD  - Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 
      4N1, Canada.
LA  - eng
GR  - 10015088/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211124
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Bungarotoxins)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Synaptotagmin I)
RN  - 0 (Syt1 protein, mouse)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
SB  - IM
MH  - Animals
MH  - Bungarotoxins/metabolism
MH  - CA1 Region, Hippocampal/*metabolism
MH  - Disks Large Homolog 4 Protein/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - *Memory
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurogenesis
MH  - Neurons/*metabolism
MH  - Organ Specificity
MH  - Phenotype
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Synapses/metabolism
MH  - Synaptotagmin I/metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/*metabolism
MH  - Mice
PMC - PMC8699470
OTO - NOTNLM
OT  - brain connectivity
OT  - extracellular activity
OT  - learning and memory
OT  - menin
OT  - nicotinic cholinergic receptors
OT  - synaptogenesis
COIS- The authors declare no competing financial interests.
EDAT- 2021/12/25 06:00
MHDA- 2022/01/21 06:00
PMCR- 2021/11/24
CRDT- 2021/12/24 01:03
PHST- 2021/10/29 00:00 [received]
PHST- 2021/11/14 00:00 [revised]
PHST- 2021/11/17 00:00 [accepted]
PHST- 2021/12/24 01:03 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/01/21 06:00 [medline]
PHST- 2021/11/24 00:00 [pmc-release]
AID - cells10123286 [pii]
AID - cells-10-03286 [pii]
AID - 10.3390/cells10123286 [doi]
PST - epublish
SO  - Cells. 2021 Nov 24;10(12):3286. doi: 10.3390/cells10123286.