Cell death of axotomized motoneurones in neonatal rats, and its prevention by peripheral reinnervation.

Abstract

SUMMARY1. Motoneurone death induced by axotomy in the rat was studied following section of the medial gastrocnemius nerve near the muscle 4 days after birth.2. The maximum twitch tension of the medial gastrocnemius muscle achieved by motor reinnervation after section of its nerve was about 70 % of that measured on the contralateral, intact side. 3. The number of motor units counted at 35-45 days of age in the animals whose medial gastrocnemius nerves had been sectioned on day 4 was 62 % of that observed in normal rats.4. The number of medial gastrocnemius motoneurones retrogradely labelled with horseradish peroxidase (HRP) 30-40 days after section of the medial gastrocnemius nerve was 77 % of that labelled on the contralateral, intact side.5. When the medial gastrocnemius nerve had been sectioned on day 4 and prevented from peripheral reinnervation, the number of medial gastrocnemius motoneurones labelled with HRP was, on the average, only 18 % of that labelled on the control side.6. Decreased number of medial gastrocnemius motoneurones labelled with HRP following prevention of peripheral reinnervation was associated with a decrease in the neurone density of the motor cell column, indicating the occurrence of motoneurone death.7. The majority of medial gastrocnemius motoneurones axotomized 4 days after birth appear to maintain their survival for about 2 weeks without target contact.8. The area of the compound action potential of medial gastrocnemius motor fibres once decreased after axotomy on day 4 began to recover from the 12th day after the operation if reinnervation by the cut peripheral nerve had been allowed, whereas the compound action potential continued to decrease in those axotomized motoneurones whose reinnervation had been prevented.9. It is concluded that target dependence of motoneurone survival previously observed at embryonic stages is still present during the early post-natal period.

The dependence of motoneurons on their target muscle during postnatal development of the mouse

“…However, when the period of deprivation was more extensive, as it was when the nerve was cut, almost half of the biceps' motoneurons were lost and microglial cells became labeled. Our findings support the results of Kashihara et al (1987) in that contact with the target is required for motoneuron survival and that there is a critical period after axotomy during which these motoneurons must regain target access in order to avert their death.…”

“…In particular, the target organ may continue to be important for the survival and maintenance of neurons during postnatal development. The contribution of the target to neuronal survival has been assessed in neonatal rats by examining axotomized motoneurons that were either allowed to reinnervate their former target or deliberately prevented from doing so (Kashihara et al, 1987). When target access was prevented, a substantial number of motoneurons died.…”

Exercise-Induced Activation of NMDA Receptor Promotes Motor Unit Development and Survival in a Type 2 Spinal Muscular Atrophy Model Mouse

“…During the development of the nervous system, the apparently spontaneous cell death of spinal motor neurons is a commonly occurring phenomenon that is, in all likelihood, determined by the presence and the size of their peripheral targets (Hamburger, 1958;Tanaka and Landmesser, 1986). Although this natural event in the spinal cord is no longer observed after birth in rat and mouse (Oppenheim, 1991), both motor neurons and sensory neurons undergo apoptosis after experiments of target deprivation or peripheral nerve axotomy in the neonates (Kashihara et al, 1987). The dying predisposition of embryonic and neonatal motor neurons during development suggests a greater sensitivity to cell death unlike adult motor neurons, which are capable of resisting an apoptotic stimulus.…”

Electrophysiological properties of axotomized facial motoneurones that are destined to die in neonatal rats.

“…In neonatal animals, a large number of motoneurones die after axotomy with a relatively short time course (Romanes, 1946;Schmalbruch, 1984;Kashihara, Kuno & Miyata, 1987;Lowrie, Krishnan & Vrbova, 1987;Snider & Thanedar, 1989;Crew & Wigston, 1990). For example, about 80 % of facial motoneurones die within 1 week when the facial nerve is injured in neonatal rats (Sendtner, Kreutzberg & Thoenen, 1990;S0reide, 1981;see also LaVelle & LaVelle, 1958).…”