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lynx1 Supports Neuronal Health in the Mouse Dorsal Striatum During Aging: an Ultrastructural Investigation

Kobayashi, Atsuko and Parker, Rell L. and Wright, Ashley P. and Brahem, Hajer and Ku, Pauline and Oliver, Katherine M. and Walz, Andreas and Lester, Henry A. and Miwa, Julie M. (2014) lynx1 Supports Neuronal Health in the Mouse Dorsal Striatum During Aging: an Ultrastructural Investigation. Journal of Molecular Neuroscience, 53 (3). pp. 525-536. ISSN 0895-8696. PMCID PMC4265479. doi:10.1007/s12031-014-0352-1. https://resolver.caltech.edu/CaltechAUTHORS:20140721-090832827

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Abstract

Nicotinic acetylcholine receptors have been shown to participate in neuroprotection in the aging brain. Lynx protein modulators dampen the activity of the cholinergic system through direct interaction with nicotinic receptors. Although lynx1 null mutant mice exhibit augmented learning and plasticity, they also exhibit macroscopic vacuolation in the dorsal striatum as they age, detectable at the optical microscope level. Despite the relevance of the lynx1 gene to brain function, little is known about the cellular ultrastructure of these age-related changes. In this study, we assessed degeneration in the dorsal striatum in 1-, 3-, 7-, and 13-month-old mice, using optical and transmission electron microscopy. We observed a loss of nerve fibers, a breakdown in nerve fiber bundles, and a loss of neuronal nuclei in the 13-month-old lynx1 null striatum. At higher magnification, these nerve fibers displayed intracellular vacuoles and disordered myelin sheaths. Few or none of these morphological alterations were present in younger lynx1 null mutant mice or in heterozygous lynx1 null mutant mice at any age. These data indicate that neuronal health can be maintained by titrating lynx1 dosage and that the lynx1 gene may participate in a trade-off between neuroprotection and augmented learning.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1007/s12031-014-0352-1DOIArticle
http://link.springer.com/article/10.1007%2Fs12031-014-0352-1PublisherArticle
http://rdcu.be/twgaPublisherFree ReadCube access
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265479/PubMed CentralArticle
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2014 Springer Science+Business Media New York. Received: 30 August 2013; accepted: 9 June 2014. This work was supported by funds from Tobacco-Related Disease Research Program of the University of California, Grant Number TRDRP19KT-0032 for JMM and RLP, TRDRP22DT-0008 and NIH/NRSA Institutional training grant 5 T32 GM07616 for RLP; US- India BRCP Award - 1R21DA033831 for JMM; R01AG-033954 for HAL and JMM; R41DA032464 and 1R43MH094004 for PK, HB, APW and AW. Financial support for this project included funds for undergraduate research from the College of Arts & Sciences and the Department of Biological Sciences at Lehigh University for KMO. The Jensen electron microscopy facility is funded in part by the Gordon and Betty Moore Foundation, the Agouron Institute and the Beckman Foundation. Special thanks to Dr. Amber Rice for helpful discussion and critical reading of the manuscript, and to Samantha Eichelberger for editorial help. In memory of Andreas Walz.
Funders:
Funding AgencyGrant Number
California Tobacco-Related Disease Research ProgramTRDRP19KT-0032
California Tobacco-Related Disease Research ProgramTRDRP22DT-0008
NIH Predoctoral Fellowship5T32 GM07616
NIH1R21DA033831
NIHR01AG-033954
NIHR41DA032464
NIH1R43MH094004
Lehigh UniversityUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
Agouron InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
US-India Bilateral Brain Research Collaborative PartnershipsUNSPECIFIED
Subject Keywords:Nicotinic acetylcholine receptors; Cholinergic system; Prototoxins; Neurotoxins; Neurodegeneration; Plasticity; Learning and memory
Issue or Number:3
PubMed Central ID:PMC4265479
DOI:10.1007/s12031-014-0352-1
Record Number:CaltechAUTHORS:20140721-090832827
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140721-090832827
Official Citation:Kobayashi, A., Parker, R.L., Wright, A.P. et al. J Mol Neurosci (2014) 53: 525. doi:10.1007/s12031-014-0352-1
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:47358
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:21 Jul 2014 20:56
Last Modified:10 Nov 2021 17:38

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