Rescue of motoneurones by MK-801 innervating partially denervated rat muscles.
Partial denervation of the extensor digitorum longus muscle by cutting the L4 spinal nerve in 3-day-old rats causes some of the remaining uninjured motoneurones to die. A previous study has shown that of the 12 motor units usually present in the remaining uninjured L5 spinal nerve, a significantly smaller number of motor units to extensor digitorum longus muscle is found in animals operated on at 3 days. This reduction can be caused by a greater sensitivity of neonatal motoneurones with axons in a partially denervated muscle, to excitotoxic effects of glutamate. Therefore an N-methyl- D-aspartic acid (NMDA) receptor antagonist, MK-801, was injected daily for 12 days after partial denervation at 3 days. Two months after the operation contractile properties, motor unit numbers and sizes were studied. Following MK-801 treatment, the reduction in muscle weight and force output of the partially denervated muscle was less than that in the untreated group. Moreover there were more motor units in MK-801 treated animals. After partial denervation only, 15% of the total number of motor units was present whereas when the same operation was followed by treatment with MK-801, 29% remained. The mean motor unit size in the untreated group was 69% while after treatment with MK-801 it was 152% of the control. Thus treatment with MK-801 after partial denervation of neonatal animals rescued some of the motoneurones destined to die, and allowed expansion of motor unit territory of most of the surviving motoneurones.
Tyc
F
F
Department of Anatomy and Developmental Biology, Centre for Neuroscience, UCL, Gower Street, London WC1E 6BT, UK. tyc@univ-littoral.fr
Vrbová
G
G
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007839:Functional Laterality; D009046:Motor Neurons / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000294:innervation* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013127:Spinal Nerves / Q000293:injuries; D018709:Statistics, Nonparametric; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate