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Motor Neurones (motor + neurone)

Distribution by Scientific Domains

Medical Sciences	52%
Life Sciences	43%

Terms modified by Motor Neurones

motor neurone disease

Selected Abstracts

The pathophysiology of spasticity

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2002
G. Sheean
Spasticity is only one of several components of the upper motor neurone (UMN) syndrome, known collectively as the `positive' phenomena, that are characterized by muscle overactivity. Other components include tendon hyper-reflexia, clonus, the clasp-knife phenomenon, flexor and extensor spasms, a Babinski sign, and spastic dystonia. Spasticity is a form of hypertonia due to hyperexcitable tonic stretch reflexes. It is distinguished from rigidity by its dependence upon the speed of the muscle stretch and by the presence of other positive UMN signs. Hyperactive spinal reflexes mediate most of these positive phenomena, while others are due to disordered control of voluntary movement or abnormal efferent drive. An UMN lesion disturbs the balance of supraspinal inhibitory and excitatory inputs, producing a state of net disinhibition of the spinal reflexes. These include proprioceptive (stretch) and nociceptive (flexor withdrawal and extensor) reflexes. The clinical syndrome resulting from an UMN lesion depends more upon its location and extent, and the time since it occurred, than on the pathology of the lesion. However, the change in spinal reflex excitability cannot simply be due to an imbalance in supraspinal control. The delayed onset after the lesion and the frequent reduction in reflex excitability over time, suggests plasticity in the central nervous system. Knowledge of the electrophysiology and neurochemistry of spinal reflexes, together with the action of antispasticity drugs, helps us to understand the pathophysiology of spasticity. [source]

OLIG-1 and 2 gene expression and oligodendroglial tumours

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2002
K. Hoang-Xuan
OLIG 1/2 genes encode basic helix-loop-helix transcription factors that play a critical role in motor neurone and oligodendrocyte fate specification during development. Two recent studies in which OLIG transcripts were detected by in situ hybridization have reported a high expression of the OLIG genes in oligodendrogliomas. This suggests that the detection of these lineage markers could become an adjunct to the classic morphological diagnosis of these tumours. There are problems in the diagnosis of oligodendroglioma. To date, all other known oligodendrocyte lineage markers have failed to label specifically neoplastic oligodendrocytes. Deletions on chromosome 1p and 19q are much more frequent in oligodendrogliomas than in astrocytomas but these molecular alterations are not constant. For the future, when routinely available, immunohistochemical techniques using anti-OLIG antibodies on paraffin embedded tissues will allow a systematic study of a large series of tumours so that we will know the specificity and sensitivity of this investigation in diagnosis. At another level, it is possible that expression of OLIG in neoplastic oligodendrocyte might participate in the oncogenesis of oligodendrogliomas. Initial work suggests that this is probably not the case. However further in vitro and in vivo studies analysing the functional consequence of OLIG overexpression in terms of proliferation and tumour progression are needed. [source]

Synchronization of enteric neuronal firing during the murine colonic MMC

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
Nick J. Spencer
DiI (1,1,didodecyl-3,3,3,,3,-tetramethylindocarbecyanine perchlorate) retrograde labelling and intracellular electrophysiological techniques were used to investigate the mechanisms underlying the generation of spontaneously occurring colonic migrating myoelectric complexes (colonic MMCs) in mice. In isolated, intact, whole colonic preparations, simultaneous intracellular electrical recordings were made from pairs of circular muscle (CM) cells during colonic MMC activity in the presence of nifedipine (1,2 ,m). During the intervals between colonic MMCs, spontaneous inhibitory junction potentials (IJPs) were always present. The amplitudes of spontaneous IJPs were highly variable (range 1,20 mV) and occurred asynchronously in the two CM cells, when separated by 1 mm in the longitudinal axis. Colonic MMCs occurred every 151 ± 7 s in the CM and consisted of a repetitive discharge of cholinergic rapid oscillations in membrane potential (range: 1,20 mV) that were superimposed on a slow membrane depolarization (mean amplitude: 9.6 ± 0.5 mV; half-duration: 25.9 ± 0.7 s). During the rising (depolarizing) phase of each colonic MMC, cholinergic rapid oscillations occurred simultaneously in both CM cells, even when the two electrodes were separated by up to 15 mm along the longitudinal axis of the colon. Smaller amplitude oscillations (< 5 mV) showed poor temporal correlation between two CM cells, even at short electrode separation distances (i.e. < 1 mm in the longitudinal axis). When the two electrodes were separated by 20 mm, all cholinergic rapid oscillations and IJPs in the CM (regardless of amplitude) were rarely, if ever, coordinated in time during the colonic MMC. Cholinergic rapid oscillations were blocked by atropine (1 ,m) or tetrodotoxin (1 ,m). Slow waves were never recorded from any CM cells. DiI labelling showed that the maximum projection length of CM motor neurones and interneurones along the bowel was 2.8 mm and 13 mm, respectively. When recordings were made adjacent to either oral or anal cut ends of the colon, the inhibitory or excitatory phases of the colonic MMC were absent, respectively. In summary, during the colonic MMC, cholinergic rapid oscillations of similar amplitudes occur simultaneously in two CM cells separated by large distances (up to 15 mm). As this distance was found to be far greater than the projection length of any single CM motor neurone, we suggest that the generation of each discrete cholinergic rapid oscillation represents a discreet cholinergic excitatory junction potential (EJP) that involves the synaptic activation of many cholinergic motor neurones simultaneously, by synchronous firing in many myenteric interneurones. Our data also suggest that ascending excitatory and descending inhibitory nerve pathways interact and reinforce each other. [source]

Changes in presumed motor cortical activity during fatiguing muscle contraction in humans

ACTA PHYSIOLOGICA, Issue 3 2010
T. Seifert
Abstract Aim:, Changes in sensory information from active muscles accompany fatiguing exercise and the force-generating capacity deteriorates. The central motor commands therefore must adjust depending on the task performed. Muscle potentials evoked by transcranial magnetic stimulation (TMS) change during the course of fatiguing muscle activity, which demonstrates activity changes in cortical or spinal networks during fatiguing exercise. Here, we investigate cortical mechanisms that are actively involved in driving the contracting muscles. Methods:, During a sustained submaximal contraction (30% of maximal voluntary contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At an intensity below motor threshold, TMS reduced the ongoing muscle activity in biceps brachii. This reduction appears as a suppression at short latency of the stimulus-triggered average of rectified electromyographic (EMG) activity. The magnitude of the suppression was evaluated relative to the mean EMG activity during the 50 ms prior to the cortical stimulus. Results:, During the first 2 min of the fatiguing muscle contraction the suppression was 10 ± 0.9% of the ongoing EMG activity. At 2 min prior to task failure the suppression had reached 16 ± 2.1%. In control experiments without fatigue we did not find a similar increase in suppression with increasing levels of ongoing EMG activity. Conclusion:, Using a form of TMS which reduces cortical output to motor neurones (and disfacilitates them), this study suggests that neuromuscular fatigue increases this disfacilitatory effect. This finding is consistent with an increase in the excitability of inhibitory circuits controlling corticospinal output. [source]

Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neurones

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005
I. Rivera-Arconada
Abstract M-currents have been shown to control neuronal excitability in a variety of central and peripheral neurones. Here we studied the effects of specific M-current modulators on the excitability of spinal neurones and their response to synaptic activation. Experiments were performed in vitro using the hemisected spinal cord from 7- to 11-day-old rats. Intracellular recordings were obtained from lumbar deep dorsal horn and motor neurones. Neuronal excitability was assessed by applying outward current pulses and synaptic responses were elicited by activation of a lumbar dorsal root. The M-current antagonist 10,10- bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991) and the agonist retigabine were superfused at 10 µm. Retigabine produced hyperpolarization and a large decrease in the excitability of motor (7/7) and dorsal horn neurones (11/12). The effects of retigabine were fully reversed by XE-991. XE-991 induced depolarization of most neurones tested and a large increase in the excitability of motor neurones (7/7) but only a weak increase in the excitability of a proportion of dorsal horn neurones (4/10). The effects of XE-991 were partly reversed by retigabine. Consistent with their effects on neuronal excitability, retigabine showed a general depressant effect on synaptic transmission, whereas XE-991 showed the opposite tendency to potentiate responses to dorsal root stimulation, particularly in motor neurones. The results show that retigabine can depress spinal excitability and the transmission of nociceptive information. Results also indicate a post-synaptic expression of functional M-currents in most motor neurones and a considerable proportion of deep dorsal horn neurones. [source]

Uncoupling of rhythmic hypoglossal from phrenic activity in the rat

EXPERIMENTAL PHYSIOLOGY, Issue 6 2004
Walter M. St.-John
During eupnoea, rhythmic motor activities of the hypoglossal, vagal and phrenic nerves are linked temporally. The inspiratory discharges of the hypoglossal and vagus motor neurones commence before the onset of the phrenic burst. The vagus nerve also discharges in expiration. Upon exposure to hypocapnia or hypothermia, the hypoglossal discharge became uncoupled from that of the phrenic nerve. This uncoupling was evidenced by variable times of onset of hypoglossal discharge before or after the onset of phrenic discharge, extra bursts of hypoglossal activity in neural expiration, or complete absence of any hypoglossal discharge during a respiratory cycle. No such changes were found for vagal discharge, which remained linked to the phrenic bursts. Intracellular recordings in the hypoglossal nucleus revealed that all changes in hypoglossal discharge were due to neuronal depolarization. These results add support to the conclusion that the brainstem control of respiratory-modulated hypoglossal activity differs from control of phrenic and vagal activity. These findings have implications for any studies in which activity of the hypoglossal nerve is used as the sole index of neural inspiration. Indeed, our results establish that hypoglossal discharge alone is an equivocal index of the pattern of overall ventilatory activity and that this is accentuated by hypercapnia and hypothermia. [source]

Medullary motor neurones associated with drinking behaviour of Japanese eels

JOURNAL OF FISH BIOLOGY, Issue 1 2003
T. Mukuda
A fluorescent dye, Evans blue (EB), was injected into the following seven drinking-associated muscles of the Japanese eel Anguilla japonica: the sternohyoid, third branchial, fourth branchial, opercular, pharyngeal, upper oesophageal sphincter and oesophageal body muscles. The sternohyoid muscle promotes ,ingestion', and the remaining muscles contribute to ,swallowing'. All neurones stained by EB were located ipsilaterally in the caudal medulla oblongata (MO) of the Japanese eel. Neurones projecting into the sternohyoid muscle were identified as those in the spino-occipital motor nucleus (NSO), and neurones projecting into the remaining muscles as those in the glossopharyngeal,vagal motor complex (GVC). Within the GVC, the neuronal arrangement was topological, and hence, ,swallowing' will be completed if the GVC neurones ,fire' progressively from rostral to caudal. These neurones in the NSO and GVC may use acetylcholine (ACh) as a neurotransmitter, as the EB-positive neurones in both nuclei were immunoreactive against anticholine acetyltransferase (anti-ChAT) antibody. Besides the MO, some somata in a ganglion of the vagal nerve were also stained by EB injected into the pharyngeal, the upper oesophageal sphincter and the oesophageal body muscles. The localization and the shape of the somata suggest that they are sensory neurones. These sensory neurones were not ChAT-immunoreactive. Combining these results, based on a model for ,swallowing' in mammals, a plausible model for central organization of ,drinking' in the Japanese eel is proposed, which suggests that ,drinking' in the fishes is regulated by the neuronal circuit for ,swallowing' in mammals. [source]

Loss of metabotropic glutamate receptor-mediated regulation of glutamate transport in chemically activated astrocytes in a rat model of amyotrophic lateral sclerosis

JOURNAL OF NEUROCHEMISTRY, Issue 3 2006
Céline Vermeiren
Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a selective loss of motor neurones accompanied by intense gliosis in lesioned areas of the brain and spinal cord. Glutamate-mediated excitotoxicity resulting from impaired astroglial uptake constitutes one of the current pathophysiological hypotheses explaining the progression of the disease. In this study, we examined the regulation of glutamate transporters by type 5 metabotropic glutamate receptor (mGluR5) in activated astrocytes derived from transgenic rats carrying an ALS-related mutated human superoxide dismutase 1 (hSOD1G93A) transgene. Cells from transgenic animals and wild-type littermates showed similar expression of glutamate,aspartate transporter and glutamate transporter 1 (GLT-1) after in vitro activation, whereas cells carrying the hSOD1 mutation showed a three-fold higher expression of functional mGluR5, as observed in the spinal cord of end-stage animals. In cells from wild-type animals, (S)-3,5-dihydroxyphenylglycine (DHPG) caused an immediate protein kinase C (PKC)-dependent up-regulation of aspartate uptake that reflected the activation of GLT-1. Although this effect was mimicked in both cultures by direct activation of PKC using phorbol myristate acetate, DHPG failed to up-regulate aspartate uptake in cells derived from the transgenic rats. The failure of activated mGluR5 to increase glutamate uptake in astrocytes derived from this animal model of ALS supports the theory of glutamate excitotoxicity in the pathogenesis of the disease. [source]

Androgen-induced neurite outgrowth is mediated by neuritin in motor neurones

JOURNAL OF NEUROCHEMISTRY, Issue 1 2005
T. U. Marron
Abstract In the brain, the spinal cord motor neurones express the highest levels of the androgen receptor (AR). Experimental data have suggested that neurite outgrowth in these neurones may be regulated by testosterone or its derivative 5,-dihydrotestosterone (DHT), formed by the 5,-reductase type 2 enzyme. In this study we have produced and characterized a model of immortalized motor neuronal cells expressing the mouse AR (mAR) [neuroblastoma-spinal cord (NSC) 34/mAR] and analysed the role of androgens in motor neurones. Androgens either activated or repressed several genes; one has been identified as the mouse neuritin, a protein responsible for neurite elongation. Real-time PCR analysis has shown that the neuritin gene is expressed in the basal condition in immortalized motor neurones and is selectively up-regulated by androgens in NSC34/mAR cells; the DHT effect is counteracted by the anti-androgen Casodex. Moreover, DHT induced neurite outgrowth in NSC34/mAR, while testosterone was less effective and its action was counteracted by the 5,-reductase type 2 enzyme inhibitor finasteride. Finally, the androgenic effect on neurite outgrowth was abolished by silencing neuritin with siRNA. Therefore, the trophic effects of androgens in motor neurones may be explained by the androgenic regulation of neuritin, a protein linked to neurone development, elongation and regeneration. [source]

Lower oesophageal sphincter relaxation evoked by stimulation of the dorsal motor nucleus of the vagus in ferrets

NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2002
T. P. Abrahams
Abstract, An understanding of the neural control of lower oesophageal sphincter (LOS) relaxation is clinically relevant because transient LOS relaxations (TLOSRs) are a mechanism of acid reflux into the oesophagus. Preganglionic motor neurones innervating the LOS are localized in the dorsal motor nucleus of the vagus (DMV). Based on a single study in cats, it is now widely accepted that these neurones are functionally organized into two separate populations, such that stimulation of the caudal and rostral DMV evokes LOS relaxation and contraction, respectively. Our goal was to map the functional LOS responses to chemical stimulation in the DMV and nucleus tractus solitarius (NTS) of ferrets, an animal model commonly used for conscious studies on TLOSRs, and to test whether DMV-evoked LOS relaxation is mediated through hexamethonium-sensitive vagal-inhibitory pathways to the LOS. We used miniaturized manometry with Dentsleeve to monitor LOS and oesophageal pressures in decerebrate unanaesthetized ferrets. LOS relaxation was evoked readily in response to gastric insufflation, which shows that the vago,vagal reflex was intact in this preparation. Microinjections of l -glutamate (12.5 nmol L,1in 25 nL) were made into the DMV from approximately ,,1.5 to +,2.0 mm relative to the obex. Microinjections into the caudal (, 1.5 to +,0.0 mm behind obex) and intermediate (+ 0.1 to +,1.0 mm rostral to obex) DMV both significantly decreased LOS pressure, and complete LOS relaxation was noted in 28/32 and 11/18 cases, respectively. LOS relaxation responses to DMV microinjection were highly reproducible and abolished by bilateral vagotomy or hexamethonium (15 mg kg,1intravenously). A nitric oxide synthase inhibitor (l -NAME 100 mg kg,1intramuscularly) significantly increased the time taken to reach the maximal response. Increases in LOS pressure (24 ± 4 mmHg; n = 3) were obtained only when stimulation sites were located equal to greater than 1.5 mm rostral to the obex. LOS relaxation (, 78 ± 10%; n = 6) was evoked by stimulation of the NTS but not immediately outside of the NTS (11 ± 27%; n = 5). We conclude that there is a very extensive population of ,inhibitory' motor neurones in the DMV that may account for the predominant vagal-inhibitory tone in ferrets. As NTS stimulation evokes LOS relaxation and the predominant response to DMV stimulation is also LOS relaxation, this vago,vagal reflex may involve an excitatory interneurone between the NTS and DMV vagal inhibitory output. [source]

Evidence for functional NK1 -tachykinin receptors on motor neurones supplying the circular muscle of guinea-pig small and large intestine

NEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2000
Bian
The guinea-pig intestine was investigated to determine which neurones are excited via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]-SP and septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)-insensitive mechanism. In the proximal colon, they also evoked a TTX-sensitive relaxation; in the distal colon, the contractions were larger when nerve impulses were blocked with TTX, indicating that the agonists excited inhibitory motor neurones. In the duodenum and ileum, TTX reduced agonist-evoked contractions indicating that excitatory motor neurones were activated. In the presence of indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these agonists suggesting that NK1 receptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circular muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the duodenum and distal colon. As reported previously for the ileum,1 some neurones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are functional NK1 receptors on excitatory and inhibitory motor neurones in the guinea-pig small intestine and on inhibitory motor neurones in the colon. [source]

Differences in circular muscle contraction and peristaltic motor inhibition caused by tachykinin NK1 receptor agonists in the guinea-pig small intestine

NEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2000
Shahbazian
The tachykinin NK1 receptor agonist substance P methyl ester (SPOME) impedes intestinal peristalsis by releasing nitric oxide (NO) from inhibitory motor neurones. Since NK1 receptor agonists differ in their receptor interaction, we set out to compare a range of NK1 receptor agonists including SPOME, septide and GR-73 632 in their effects on propulsive peristalsis and circular muscle activity in the guinea-pig isolated small intestine. SPOME (100,300 n M) inhibited peristalsis by a rise of the pressure threshold at which peristaltic waves were triggered, whereas septide and GR-73 632 (30,300 n M) interrupted peristalsis by causing circular muscle spasms. Separate experiments showed that all three NK1 receptor agonists caused contraction of the circular muscle, which was enhanced by the NO synthase inhibitor NG -nitro- L -arginine methyl ester (300 ,M) and the P2X purinoceptor antagonist suramin (300 ,M). In contrast, tetrodotoxin (300 n M) augmented the contractile effect of septide and GR-73 632 but not that of SPOME. It is concluded that the motor response to NK1 receptor agonists involves release of NO and adenosine triphosphate from inhibitory motor neurones. However, the NK1 receptor agonists differ in the mechanism by which they cause inhibitory transmitter release, which corresponds to differences in their antiperistaltic action. [source]

Parkinson's disease: a dual-hit hypothesis

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2007
C. H. Hawkes
Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non-motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose , hence the term ,dual-hit'. [source]

Embryonic stem cells and prospects for their use in regenerative medicine approaches to motor neurone disease

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2007
Y. A. Christou
Human embryonic stem cells are pluripotent cells with the potential to differentiate into any cell type in the presence of appropriate stimulatory factors and environmental cues. Their broad developmental potential has led to valuable insights into the principles of developmental and cell biology and to the proposed use of human embryonic stem cells or their differentiated progeny in regenerative medicine. This review focuses on the prospects for the use of embryonic stem cells in cell-based therapy for motor neurone disease or amyotrophic lateral sclerosis, a progressive neurodegenerative disease that specifically affects upper and lower motor neurones and leads ultimately to death from respiratory failure. Stem cell-derived motor neurones could conceivably be used to replace the degenerated cells, to provide authentic substrates for drug development and screening and for furthering our understanding of disease mechanisms. However, to reliably and accurately culture motor neurones, the complex pathways by which differentiation occurs in vivo must be understood and reiterated in vitro by embryonic stem cells. Here we discuss the need for new therapeutic strategies in the treatment of motor neurone disease, the developmental processes that result in motor neurone formation in vivo, a number of experimental approaches to motor neurone production in vitro and recent progress in the application of stem cells to the treatment and understanding of motor neurone disease. [source]

Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophy

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2007
H. Adachi
Spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease is a motor neurone disease characterized by muscle atrophy, weakness, contraction fasciculations and bulbar involvement. SBMA mainly affects males, while females are usually asymptomatic. SBMA is caused by expansion of a polyglutamine (polyQ)-encoding CAG trinucleotide repeat in the androgen receptor (AR) gene. AR belongs to the heat shock protein 90 (Hsp90) client protein family. The histopathologic hallmarks of SBMA are diffuse nuclear accumulation and nuclear inclusions of the mutant AR with expanded polyQ in residual motor neurones in the brainstem and spinal cord as well as in some other visceral organs. There is increasing evidence that the ligand of AR and molecular chaperones play a crucial role in the pathogenesis of SBMA. The success of androgen deprivation therapy in SBMA mouse models has been translated into clinical trials. In addition, elucidation of its pathophysiology using animal models has led to the development of disease-modifying drugs, that is, Hsp90 inhibitor and Hsp inducer, which inhibit the pathogenic process of neuronal degeneration. SBMA is a slowly progressive disease by nature. The degree of nuclear accumulation of mutant AR in scrotal skin epithelial cells was correlated with that in spinal motor neurones in autopsy specimens; therefore, the results of scrotal skin biopsy may be used to assess the efficacy of therapeutic trials. Clinical and pathological parameters that reflect the pathogenic process of SBMA should be extensively investigated. [source]

Expression of peripherin in the brain of macaques (Macaca mulatta and Macaca fascicularis) occurs in astrocytes rather than neurones and is associated with encephalitis

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2001
J. S. Mathew
Peripherin is a member of the type III intermediate filament family, expressed in neurones of the peripheral nervous system of many species and in a discrete subpopulation of neurones of the central nervous system (CNS) during early development in rodents. Previous studies on rats have shown that peripherin immunoreactivity increased significantly in cell bodies of spinal motor neurones following axonal injury. Our study examined the expression of peripherin in the cerebrum of normal macaques (Macaca mulatta and Macaca fascicularis) and those with encephalitis of viral (simian immunodeficiency virus and simian virus 40) or autoimmune (experimental allergic encephalomyelitis) aetiology. Immunohistochemistry, immunoelectronmicroscopy, immunofluorescence and confocal microscopy were performed on tissue sections using antibodies against cell-specific markers and peripherin. Peripherin-positive cells were absent in the cerebrum of normal macaques of all ages examined, whereas animals with encephalitis had peripherin-positive cells associated with inflammatory infiltrates. Further evaluation revealed that these peripherin-positive cells were not neurones, but were predominantly astrocytes expressing glial fibrillary acidic protein. Our study suggests that peripherin is not neurone-specific in the CNS of macaques; peripherin is expressed in astrocytes of animals with encephalitis. [source]

Apoptosis in amyotrophic lateral sclerosis: a review of the evidence

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2001
S. Sathasivam
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting the upper and lower motor neurones of the central nervous system. Recently, a lot of interest has been generated by the possibility that a mechanism of programmed cell death, termed apoptosis, is responsible for the motor neurone degeneration in this condition. Apoptosis is regulated through a variety of different pathways which interact and eventually lead to controlled cell death. Apart from genetic regulation, factors involved in the control of apoptosis include death receptors, caspases, Bcl-2 family of oncoproteins, inhibitor of apoptosis proteins (IAPs), inhibitors of IAPs, the p53 tumour suppressor protein and apoptosis-related molecules. The first part of this article will give an overview of the current knowledge of apoptosis. In the second part of this review, we will examine in detail the evidence for and against the contribution of apoptosis in motor neurone cell death in ALS, looking at cellular-, animal- and human post-mortem tissue-based models. In a chronic neurodegenerative disease such as ALS, conclusive evidence of apoptosis is likely to be difficult to detect, given the rapidity of the apoptotic cell death process in relation to the relatively slow time course of the disease. Although a complete picture of motor neurone death in ALS has not been fully elucidated, there is good and compelling evidence that a programmed cell death pathway operates in this disorder. The strongest body of evidence supporting this comes from the findings that, in ALS, changes in the levels of members of the Bcl-2 family of oncoproteins results in a predisposition towards apoptosis, there is increased expression or activation of caspases-1 and -3, and the dying motor neurones in human cases exhibit morphological features reminiscent of apoptosis. Further supporting evidence comes from the detection of apoptosis-related molecules and anti-Fas receptor antibodies in human cases of ALS. However, the role of the p53 protein in cell death in ALS is at present unclear. An understanding of the mechanism of programmed cell death in ALS may provide important clues for areas of potential therapeutic intervention for neuroprotection in this devastating condition. [source]