MHCI promotes developmental synapse elimination and aging-related synapse loss at the vertebrate neuromuscular junction.

TitleMHCI promotes developmental synapse elimination and aging-related synapse loss at the vertebrate neuromuscular junction.
Publication TypeJournal Article
Year of Publication2016
AuthorsTetruashvily, MM, McDonald, MA, Frietze, KK, Boulanger, LM
JournalBrain Behav Immun
Volume56
Pagination197-208
Date Published2016 Aug
ISSN1090-2139
KeywordsAging, Animals, Animals, Newborn, Genes, MHC Class I, Mice, Neuromuscular Junction, Synapses
Abstract

<p>Synapse elimination at the developing neuromuscular junction (NMJ) sculpts motor circuits, and synapse loss at the aging NMJ drives motor impairments that are a major cause of loss of independence in the elderly. Here we provide evidence that at the NMJ, both developmental synapse elimination and aging-related synapse loss are promoted by specific immune proteins, members of the major histocompatibility complex class I (MHCI). MHCI is expressed at the developing NMJ, and three different methods of reducing MHCI function all disrupt synapse elimination during the second postnatal week, leaving some muscle fibers multiply-innervated, despite otherwise outwardly normal synapse formation and maturation. Conversely, overexpressing MHCI modestly accelerates developmental synapse elimination. MHCI levels at the NMJ rise with aging, and reducing MHCI levels ameliorates muscle denervation in aged mice. These findings identify an unexpected role for MHCI in the elimination of neuromuscular synapses during development, and indicate that reducing MHCI levels can preserve youthful innervation of aging muscle. </p>

DOI10.1016/j.bbi.2016.01.008
Alternate JournalBrain Behav. Immun.
PubMed ID26802986
PubMed Central IDPMC5813483
Grant ListF30 AG046044 / AG / NIA NIH HHS / United States