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

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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.

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Support Acknowledgments

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 5T32 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 discussions and critical reading of the manuscript. In memory of Andreas Walz.

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Authors and Affiliations

  1. Biology Division, California Institute of Technology, MC156-29, 1200 E. California Blvd., Pasadena, CA, 91125, USA

    Atsuko Kobayashi, Rell L. Parker, Henry A. Lester & Julie M. Miwa

  2. Tokyo Institute of Technology, Earth-Life Science Institute, 2-12-1 IE-31 Ookayama, Meguro-ku, Tokyo, 152-8551, Japan

    Atsuko Kobayashi

  3. Ophidion, Inc, 2265 E. Foothill Blvd., Pasadena, CA, 91107, USA

    Ashley P. Wright, Hajer Brahem, Pauline Ku & Andreas Walz

  4. Department of Biological Sciences, Lehigh University, Iacocca Hall B217, 111 Research Dr., Bethlehem, PA, 18015, USA

    Katherine M. Oliver & Julie M. Miwa

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  1. Atsuko Kobayashi
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  2. Rell L. Parker
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Correspondence to Julie M. Miwa.

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Kobayashi, A., Parker, R.L., Wright, A.P. et al. lynx1 Supports Neuronal Health in the Mouse Dorsal Striatum During Aging: an Ultrastructural Investigation. J Mol Neurosci 53, 525–536 (2014). https://doi.org/10.1007/s12031-014-0352-1

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  • DOI: https://doi.org/10.1007/s12031-014-0352-1

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