Denervation of primate extraocular muscle. A unique pattern of structural alterations

Department of Anatomy, University of Mississippi Medical Center, Jackson 39216.
Investigative Ophthalmology & Visual Science (Impact Factor: 3.4). 09/1989; 30(8):1894-908.
Source: PubMed


Extraocular muscles differ from most other skeletal muscles in terms of constituent fiber types and innervation pattern. The rules that govern fiber responses to various experimental interventions for most skeletal muscles, therefore, may not strictly apply to the extraocular muscles. In this study, denervation of the extraocular muscles of Cynomolgous monkeys, Macaca fascicularis, was accomplished by intracranial transection of the oculomotor nerve. Survival times of 3-167 days were allowed, and muscles were processed for analysis by light and electron microscopy. Short-term alterations involved all muscle fiber types and included retraction of neuromuscular junctions, mild myofibril disruption and inflammatory cell infiltration. Long-term morphopathological changes were most apparent in the orbital singly innervated fiber type and its global layer counterpart. These alterations consisted of dispersion of the mitochondrial aggregates which characterize this fiber type. Only occasional fibers (all types) exhibited severe vacuolar atrophy or myofilament breakdown despite the occurrence of only limited reinnervation. When extensive reinnervation did occur, the characteristic layered organization of the extraocular muscles was preserved and fiber type grouping was not apparent. Taken together, these findings indicate that the extraocular muscles exhibit a resilience to denervation beyond that observed for other skeletal musculature.

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    • "Muscles differ in many ways that might be correlated with susceptibility, including their position along the rostrocaudal axis, whether they are innervated by spinal or cranial motor neurons, their fiber type composition, the size of their motor units and the length of the axons supplying them. Indeed, the highly susceptible EDL and the spared EOM differ in all of these respects [24], [25], [26], [27], [28]. First, we used the data in Table 1 to assess the relationship between the segmental origin of the nerves that innervate each muscle and the incidence of age-related alterations in their NMJs. "
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    ABSTRACT: Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS.
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    No preview · Article · Sep 1989 · The Journal of Comparative Neurology
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