Upadhyay, Aaradhita, Hosseinibarkooie, Seyyedmohsen, Schneider, Svenja, Kaczmarek, Anna, Torres-Benito, Laura, Mendoza-Ferreira, Natalia, Overhoff, Melina, Rombo, Roman, Grysko, Vanessa, Kye, Min Jeong ORCID: 0000-0002-1323-7256, Kononenko, Natalia L. and Wirth, Brunhilde ORCID: 0000-0003-4051-5191 (2019). Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological. Front. Molec. Neurosci., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-5099

Full text not available from this repository.

Abstract

Neurocalcin delta (NCALD) is a brain-enriched neuronal calcium sensor and its reduction acts protective against spinal muscular atrophy (SMA). However, the physiological function of NCALD and implications of NCALD reduction are still elusive. Here, we analyzed the ubiquitous Ncald knockout in homozygous (Ncald(KO/KO)) and heterozygous (Ncald(KO/WT)) mice to unravel the physiological role of NCALD in the brain and to study whether 50% NCALD reduction is a safe option for SMA therapy. We found that Ncald(KO/KO) but not Ncald(KO/WT) mice exhibit significant changes in the hippocampal morphology, likely due to impaired generation and migration of newborn neurons in the dentate gyrus (DG). To understand the mechanism behind, we studied the NCALD interactome and identified mitogen-activated protein kinase kinase kinase 10 (MAP3K10) as a novel NCALD interacting partner. MAP3K10 is an upstream activating kinase of c-Jun N-terminal kinase (JNK), which regulates adult neurogenesis. Strikingly, the JNK activation was significantly upregulated in the Ncald(KO/KO) brains. Contrary, neither adult neurogenesis nor JNK activation were altered by heterozygous Ncald deletion. Taken together, our study identifies a novel link between NCALD and adult neurogenesis in the hippocampus, possibly via a MAP3K10-JNK pathway and emphasizes the safety of using NCALD reduction as a therapeutic option for SMA.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Upadhyay, AaradhitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hosseinibarkooie, SeyyedmohsenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, SvenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaczmarek, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres-Benito, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mendoza-Ferreira, NataliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Overhoff, MelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rombo, RomanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grysko, VanessaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kye, Min JeongUNSPECIFIEDorcid.org/0000-0002-1323-7256UNSPECIFIED
Kononenko, Natalia L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirth, BrunhildeUNSPECIFIEDorcid.org/0000-0003-4051-5191UNSPECIFIED
URN: urn:nbn:de:hbz:38-156718
DOI: 10.3389/fnmol.2019.00019
Journal or Publication Title: Front. Molec. Neurosci.
Volume: 12
Date: 2019
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 1662-5099
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SPINAL MUSCULAR-ATROPHY; HIPPOCAMPAL VOLUME; SHAM CONTROL; PROTEIN; CALCIUM; BRAIN; NUSINERSEN; EXPRESSION; IDENTIFICATION; INHIBITIONMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15671

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item