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Biomedical subjects

M B Lowrie

Publications and source records attributed to M B Lowrie.

At least 37 records · Page 2Linked to original sources
PubMed1992

A postsynaptic GABA transporter in rat spinal motor neurones.

The plasma membrane uptake system for gamma-amino butyric acid (GABA) is conventionally assumed to be presynaptic, so that after release GABA could be taken up and incorporated into synaptic vesicles for re-use. Using in situ hybridization histochemistry we find that rat spinal motor neurones express GAT-1, a transporter protein for GABA, but that they do not express glutamic acid decarboxylase, the synthetic enzyme for GABA. We conclude that the uptake system is located postsynaptically in these cells. Our observation may explain previous reports where GABA has been detected immunocytochemically in motor neurones.

Animals↗
PubMed1992

Dependence of postnatal motoneurones on their targets: review and hypothesis.

Motoneurones are known to die (1) during embryonic development (naturally occurring cell death), (2) early in postnatal development after axonal injury, and (3) as a consequence of disease, such as spinal muscular atrophy or (in later life) amyotrophic lateral sclerosis. Naturally occurring motoneurone death has been extensively investigated, and interaction with the target muscle has emerged as an important factor for survival of embryonic motoneurones. Evidence that this target dependence of motoneurones continues postnatally is discussed in this review, as is the possible nature of the retrograde signal from the muscle. An explanation for the role of the muscle in motoneurone survival is also proposed, which may be applicable in situations where motoneurone death occurs postnatally. This proposal takes into account the changing functional demands imposed on motoneurones as a result of the gradual maturation of the CNS, and suggests that during development the muscle induces the motoneurones to become competent to carry out these requirements.

Animals↗
PubMed1991

Absence of Nerve - muscle Interaction Influences the Survival of Developing Motoneurons.

Following sciatic nerve crush at birth, approximately 70% of motoneurons to the soleus and 60% of motoneurons to the tibialis anterior (TA) and to the extensor digitorum longus (EDL) die. However, following nerve injury at 5 days, there is negligible motoneuron death. We investigated whether the interaction between the nerve and its target during these 5 days is an important factor for the ability of the motoneuron to survive injury. Nerve - muscle interaction was blocked shortly after birth by alpha-bungarotoxin (BTX) and the effect on motoneuron survival after subsequent injury was examined. It was confirmed that sciatic nerve crush at 5 days produced no significant reduction in motoneuron numbers. However, if nerve crush was preceded by paralysis with alpha-bungarotoxin, the number of surviving motoneurons after nerve injury at 5 days was substantially reduced. On the operated side only 43 +/- 6.68% of the motoneurons of the soleus pool survived and even fewer, 14 +/- 5.0%, in the TA and EDL pool. In a control group of animals paralysed with alpha-bungarotoxin at birth but receiving no nerve crush, there was no appreciable reduction in the motoneuron numbers at 28 days in either motor pool. It is concluded that blocking of nerve - muscle interaction by paralysis in early postnatal life reduces the motoneurons' ability to survive nerve injury later in life, and that this effect is more severe for the motoneurons to the TA and EDL than to the soleus.

Journal Article↗
PubMed1990

Impairment of developing fast muscles after nerve injury in the rat depends upon the period of denervation.

After injury to the peripheral nerve in rat pups at 5 days of age the development of the fast muscles tibialis anterior and extensor digitorum longus is impaired. Whether the length of time during which the muscles are denervated affects the degree of impairment was studied here. In one group of animals the peroneal nerve was crushed near to the muscles in one leg and further away from the muscles in the other leg. In another group of animals the sciatic nerve was crushed in one leg at 5 days and in some of these animals the nerve was crushed again 5-7 days later. The recovery of TA and EDL was measured by recording the weight and tension developed once reinnervation was complete. When the nerve was crushed close to the muscles, the muscles recovered significantly better than when the site of injury was further away, while delaying reinnervation by crushing the sciatic nerve a second time, impaired recovery of the muscles. It is concluded that the permanent impairment of fast muscles seen after neonatal nerve injury depends upon the length of time that the muscles are separated from their motoneurones.

Animals↗
PubMed1989

The effect of load on the phenotype of the developing rat soleus muscle.

In newborn Wistar rats the load on the soleus muscle was reduced by removing the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles. Eighteen days later the soleus muscles were removed from both the operated and control legs and examined physiologically and histologically. The time course of twitch contraction of the soleus on the operated side was not significantly different from that of control muscles, but the muscles developed less tension. The decreased tension was consistent with a smaller number of muscle fibres. Histochemical and immunocytochemical examination showed that in the operated muscle, fewer fibres reacted with an antibody against slow myosin, while the number of fibres that reacted for alkali-preincubated ATPase, indicative of neonatal or adult fast myosin, was increased. Some fibres expressed both types of myosin. These findings suggest that a reduced load delays the phenotypic expression of slow myosin isoform in the developing soleus muscle.

Animals↗
PubMed1988

Reorganization of synaptic inputs to developing skeletal muscle fibres.

During early stages of postnatal development skeletal muscle fibres of mammals are contacted by several axons. The transition from poly- to mononeuronal innervation has been extensively studied on the rat soleus. The role of activity in this process has been acknowledged but the mechanisms leading to synapse remodelling are not understood. The participation of the muscle has to be taken into account; if muscles are paralysed by alpha-bungarotoxin, the elimination of terminals is arrested. Changes in Ca2+ also influence the rate of removal of terminals. Calcium seems to act through a calcium-activated neutral protease (CANP) present in nerve endings. If CANP is inhibited, elimination fails to take place. Thus Ca2+ enters the terminal and activates the CANP. Release of K+ ions from active muscle could link muscle activity and synapse elimination. Excess K+ was found to reduce nerve-muscle contacts, by depolarizing terminals and allowing Ca2+ entry. A greater increase of Ca2+ concentration in smaller terminals would be expected, because of their surface-to-volume ratio, and they are preferentially eliminated. Thus elimination depends on the unequal size of terminals at the endplate. Therefore the 'survivability' of individual nerve endings may already be determined at the time of synapse elimination.

Acetylcholine↗
PubMed1988

The distribution of slow myosin in rat muscles after neonatal nerve crush.

Following neonatal nerve injury fast skeletal muscles recover less well than slow ones. This is because many muscle fibers are lost during reinnervation. Since fast muscles normally contain a small population of slow muscle fibers, we have used a monoclonal antibody to slow myosin heavy chains (SMHC) to study their number and pattern of distribution in fast muscles following temporary denervation at 5-6 days of age and subsequent reinnervation. During this time the original distribution of slow fibers changed to one showing irregular grouping, indicating that reinnervation of muscles after neonatal nerve injury is as nonselective as it is after nerve injury in adults. Despite a large reduction in the total number of muscle fibers during reinnervation, the number of slow fibers did not decrease. Thus muscle fiber loss was at the expense of the fast motor units alone.

Animals↗
PubMed1988

Reorganization of motor units in reinnervated muscles of the rat.

Changes in motor unit organisation following nerve injury in adult and neonatal rats were compared. Motor units were studied in extensor digitorum longus muscles reinnervated after nerve injury in either neonatal or adult rats. The force developed by individual motor units was measured by stimulating ventral root filaments. After nerve section in adult rats the distribution of motor unit force was restored to normal but this did not occur following nerve crush in neonatal animals. Thus following nerve injury during the neonatal period the muscles were not only permanently weaker, but the distribution of motor unit sizes was also abnormal. Muscle fibres belonging to a single motor unit were identified histologically by the glycogen depletion method, and their fibre type and cross-sectional area measured. Although all the fibres of the same unit became histochemically homogeneous, they showed greater variation in size than normal units, suggesting that factors other than the influence of the axons control the size of muscle fibres.

Animals↗
PubMed1987

Permanent changes in muscle and motoneurones induced by nerve injury during a critical period of development of the rat.

The sciatic nerve was crushed in rats at different times during the first two weeks after birth. Following reinnervation the recovery of the fast and slow muscles and their motoneurones was compared. The main factor affecting recovery of muscle weight and tension was the age at which the nerve was crushed; the earlier the injury the greater the impairment. However, recovery also depended upon muscle type. The fast muscles, tibialis anterior and extensor digitorum longus, always recovered less well than the slow soleus muscle. The greatest difference in recovery was seen when the nerve was crushed between 3 and 6 days of age. The fatigue resistance of fast muscles was markedly increased after nerve injury at any time during the first two postnatal weeks and was greatest when the nerve crush was done soon after birth. However, this change was not just related to muscle weakness as the increase in fatigue resistance after nerve crush at 5 and 12 days was similar regardless of the difference in recovery of the muscles. Retrograde labelling of motoneurones with HRP demonstrated that about 60-70% of motoneurones innervating fast or slow muscles were lost following sciatic nerve crush at birth. It is concluded that motoneurone loss probably accounts for most of the impairment of soleus after postnatal nerve crush but only partly explains the poor recovery of fast muscles.

Animals↗
PubMed1985

The effect of reducing the peripheral field on motoneurone development in the rat.

The tibialis anterior and extensor digitorum longus muscles of the rat were reduced in size either by crushing the sciatic nerve or by removing part of the muscle tissue during the first postnatal week. Four to 6 weeks later the number and size of the motoneurones supplying these muscles were assessed using retrograde transport of horseradish peroxidase. The pattern of synaptic connections in the muscles supplied by these motoneurones was examined 3-46 weeks after the initial operation using a combined silver cholinesterase stain. The number of labelled motoneurones was not reduced after nerve crush but was reduced to some extent after partial muscle removal. The distribution of motoneurone sizes, however, was altered by both procedures in that the largest motoneurones became smaller. In the muscle both procedures affected synaptic organization. In the case of sciatic nerve crush at 5-6 days the incidence of muscle fibres with more than one endplate and endplates contacted by more than one axon terminal was higher than in normal adult muscles. When part of the muscle was removed, the predominant feature was the persistence of a high incidence of free sprouting nerve fibres. We therefore conclude that reduction of the peripheral field during the postnatal period does affect the development of some motoneurones.

Animals↗
PubMed1985

The effect of altered peripheral field on motoneurone function in developing rat soleus muscles.

In soleus muscles of 4- to 5-day-old rats the quantum content of axon terminals from L4 spinal roots is less than half that from L5. With development the size of L4 motor units decreases and the quantum content of L4 nerves increases to become similar to that of L5 axons. During this time the overlap of territories of L4 and L5 axons is reduced from 46% at 4-6 days to 2% at 18-20 days. This reduction occurs entirely at the expense of L4 territory. Removal of the L5 ventral ramus (v.r.) at 4-6 days prevents the reduction of L4 territory so that at 18 days L4 motor units are about 4 X normal size. In spite of this enlarged peripheral field of L4 axons the quantum content of their terminals increases to normal levels. When L5 v.r. was removed at 16-18 days, i.e. when the reduction of the L4 peripheral field was complete, expansion of L4 motor units was also seen, but in this case the quantum content of L4 terminals was less than normal. Thus it appears that during early stages of development, before synaptic reorganization within the muscle is complete, motoneurones are able to adapt their function to increased peripheral demands more effectively than at later stages of post-natal development. Retrograde labelling of soleus motor pool with horseradish peroxidase (HRP) showed that removal of L5 v.r. either at 4 or 15 days of age reduced the number of motoneurones supplying soleus muscle to less than 20%. No change in size of the remaining motoneurones was seen, indicating that the adjustment of transmitter output at the neuromuscular junctions in the younger group had no effect on the size of the cell.

Animals↗
PubMed1984

Different pattern of recovery of fast and slow muscles following nerve injury in the rat.

The sciatic nerve was crushed in 5-6-day-old rats and the time course of recovery and changes in physiological and morphological properties of reinnervated fast and slow muscles was compared. The maximal tetanic tension developed by the reinnervated muscles was recorded at different times from about 18 days of age, when functional recovery was first seen, until 2 months. The maximal indirectly elicited tetanic tension of the reinnervated slow soleus muscle gradually increased from 55% of normal at 18 days to 75% of normal at 2 months. In contrast, the tension of the reinnervated fast muscle extensor digitorum longus (e.d.l.) fell sharply from 70% of normal at 18 days to 40% at 21 days and remained at that level till the end of the study. The total number of muscle fibres in control, reinnervated and denervated e.d.l. muscles was counted. At 18 days the number of fibres in the reinnervated e.d.l. was similar to normal but by 1 month it had fallen to one-third. This decrease did not take place in permanently denervated muscles until at least 35 days. Loss of fibres in the reinnervated soleus was small. During the early stages of reinnervation the contraction and relaxation of the fast muscles was very prolonged. By 1 month the time taken to reach peak twitch tension had decreased to normal values but the relaxation was still slower and remained so for several months. The study of fatigue resistance showed that at 18 days the reinnervated fast muscles were as fatigable as normal muscles from animals of the same age. The fatigability of normal muscles increased with age to adult levels, but the reinnervated muscles became more fatigue resistant and remained so. Our findings suggest that fast muscles become selectively impaired after nerve injury at 6 days because they lose a large number of fibres after reinnervation.

Animals↗
PubMed1982

Recovery of slow and fast muscles following nerve injury during early post-natal development in the rat.

1. The sciatic nerve was crushed in 5-6-day-old rats and the recovery of function of slow and fast muscles was studied. The first signs of recovery of function were seen 10-12 days after the operation. 2. Maximal tetanic tension developed by the reinnervated muscles was recorded and taken as an indication of their recovery. Two months after nerve crush, slow soleus muscles developed only slightly less tension than the control unoperated soleus muscles. The reinnervated fast muscles tibialis anterior (t.a.) and extensor digitorum longus (e.d.l.) developed only about 50% of the tension of the unoperated controls. 3. The fast muscles never recovered, remaining weaker and smaller throughout the animals' life. 4. The number of muscle fibres in the reinnervated fast muscles was substantially reduced and their fibre composition altered in that they contained mainly muscle fibres with high levels of oxidative enzymes. 5. The reinnervated fast muscles became much more fatigue resistant than the unoperated controls. 6. The possibility that these changes are due to motoneurone death was examined. The motoneurones innervating the fast muscles were labelled by retrograde transport of HRP. No significant reduction in the number of motoneurones innervating the operated muscles was found. 7. These results show that nerve injury during early post-natal life causes permanent changes in fast muscles that are not caused by motoneurone death.

Animals↗
PubMed1980

The development of independent secondary ("mirror") discharges in the monkey: failure to replicate earlier findings.

Various factors that might influence the development of the independent secondary focus ("mirror" focus) in the monkey were investigated. Not 1 of 29 monkeys developed independent secondary discharges when we varied: area and length of boundary of the primary epileptogenic agent; ease of passage of agent through pia; nature of chemical agent; mechanical manipulation of homotopic cortex; or site of application of primary agent. The possible reasons for the discrepancy between this negative outcome and our earlier success in obtaining independent foci are discussed.

Aluminum Hydroxide↗
PubMed1978

The effects of ablations on primary and secondary epileptic discharges in commissure-sectioned rhesus monkeys.

Nine monkeys underwent division of the corpus callosum, anterior commissure, massa intermedia, and posterior commissure. At the same operation, in seven of these animals aluminium hydroxide was applied to the left posterior parietal-prestriate cortex. Monthly EEG recordings were taken from all animals. All seven animals with epileptogenic implants gave evidence of primary abnormal discharges (i.e. from the ipsilateral hemisphere) and secondary (i.e. from the contralateral hemisphere) discharges. The secondary events were of two types: transmitted, i.e. synchronous with primary events; independent, i.e. asynchronous with primary events. After intervals varying from 4 to 22 months all seven monkeys underwent wide ablation of the posterior parietal cortex: on the left in four animals, on the right in three animals. EEG recordings were taken for a further 6 months. All recordings were quantitatively analysed, the number of primary, transmitted secondary and independent secondary events being counted separately. This analysis indicated the following: (1) Primary and transmitted secondary discharges ceased after primary ablations but were unaffected by removal of the secondary cortex. (2) Independent secondary discharges persisted after removal of the primary focus but were abolished by secondary ablations. Possible mechanisms for the development of transmitted and independent secondary discharges are considered.

Aluminum Hydroxide↗