Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study

Stephens, Benjamin R.; Guiloff, R J; Olivares-Navarrete, René; Newman, Piers; Nikhar, Nirjal; Lewis, Paul

doi:10.1016/j.jns.2005.12.003

Cited by 90 publications

(82 citation statements)

References 88 publications

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“…Together with reports of interneuronal loss in spinal cord and cortex of human ALS patients (Maekawa et al, 2004;Stephens et al, 2006) and in transgenic mice overexpressing mutant hSOD1 (Morrison et al, 1998), this suggests that early hyperexcitability in interneurons may also contribute to interneuronal loss at later stages in ALS.…”

Section: G93a Motoneurons and Interneurons As In Fals Patients Hsod1supporting

confidence: 62%

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Zundert¹,

Peuscher²,

et al. 2008

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Distinguishing the primary from secondary effects and compensatory mechanisms is of crucial importance in understanding adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transgenic mice that overexpress the G93A mutation of the human Cu-Zn superoxide dismutase 1 gene (hSOD1 G93A mice) are a commonly used animal model of ALS. Whole-cell patch-clamp recordings from neurons in acute slice preparations from neonatal wild-type and hSOD1 G93A mice were made to characterize functional changes in neuronal activity. Hypoglossal motoneurons (HMs) in postnatal day 4 (P4)-P10 hSOD1 G93A mice displayed hyperexcitability, increased persistent Na ϩ current (PC Na ), and enhanced frequency of spontaneous excitatory and inhibitory transmission, compared with wild-type mice. These functional changes in neuronal activity are the earliest yet reported for the hSOD1 G93A mouse, and are present 2-3 months before motoneuron degeneration and clinical symptoms appear in these mice. Changes in neuronal activity were not restricted to motoneurons: superior colliculus interneurons also displayed hyperexcitability and synaptic changes (P10 -P12). Furthermore, in vivo viral-mediated GFP (green fluorescent protein) overexpression in hSOD1 G93A HMs revealed precocious dendritic remodeling, and behavioral assays revealed transient neonatal neuromotor deficits compared with controls. These findings underscore the widespread and early onset of abnormal neural activity in this mouse model of the adult neurodegenerative disease ALS, and suggest that suppression of PC Na and hyperexcitability early in life might be one way to mitigate or prevent cell death in the adult CNS.

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Section: G93a Motoneurons and Interneurons As In Fals Patients Hsod1supporting

confidence: 62%

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Zundert¹,

Peuscher²,

et al. 2008

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“…Мышечная слабость при БАС может быть обусловлена поражени-ем как верхнего, так и нижнего мотонейрона, при этом разделить вклад этих 2 составляющих часто не пред-ставляется возможным. Классические признаки пира-мидного синдрома -спастичность, сухожильная ги-перрефлексия, клонусы -могут не выявляться при выраженном поражении мотонейронов переднего рога и развившейся атрофии мышц [15,16]. Кроме того, их возникновение может быть связано не только с ослаблением влияния на сегментарный аппарат спинного мозга нисходящих двигательных путей, Оригинальные исследования но и c гибелью тормозных интернейронов в пределах спинного мозга, в частности глицинергических клеток Реншоу, что продемонстрировано в патоморфологи-ческих исследованиях [17].…”

Section: рис 2 карта коркового представительства правой M Abductorunclassified

“…Кроме того, их возникновение может быть связано не только с ослаблением влияния на сегментарный аппарат спинного мозга нисходящих двигательных путей, Оригинальные исследования но и c гибелью тормозных интернейронов в пределах спинного мозга, в частности глицинергических клеток Реншоу, что продемонстрировано в патоморфологи-ческих исследованиях [17]. Характерной особенностью БАС является редкое выявление патологического рефлекса Бабинского, он регистрируется только у 42-50 % больных [16]. Возможная причина этого -выра-женное поражение переднероговых мотонейронов мышцы-разгибателя большого пальца или преоблада-ние мышечного тонуса в сгибателях стопы и пальцев.…”

Section: рис 2 карта коркового представительства правой M Abductorunclassified

Navigated Transcranial Magnetic Stimulation Possibilities in Difficult Diagnostic Cases Upper Motor Neuron Lesions – Case Report

Bakulin¹,

Червяков²,

Zakharova³

et al. 2015

Neuromuscular Diseases

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“…3) [100,101]. Degeneration and loss of spinal and neocortical interneurons has also been found in human ALS [102,103]. More than 5000 people in the USA are diagnosed with ALS each year (ALS Association, http://www.alsa.org), and, in parts of the United Kingdom, three people die every day from some form of motor neuron disease (http://www.mndassociation.org).…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

“…It is still not understood why specific neuronal populations are selectively vulnerable in ALS, such as certain somatic motor neurons and interneurons [100][101][102][103]. The molecular pathogenesis of ALS is understood poorly, contributing to the lack of appropriate target identification and effective mechanism-based therapies to treat even the symptoms of this disease.…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Mitochondrial Pathobiology in Parkinson's Disease and Amyotrophic Lateral Sclerosis

Martin

2010

JAD

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Abstract. Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are the second and third most common human adult-onset neurodegenerative diseases, respectively, after Alzheimer's disease. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of PD and ALS are inherited, and genes causing these diseases have been identified. Morphological, biochemical, and genetic, as well as cell and animal model, studies reveal that mitochondria could have a role in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review will present how mitochondrial pathobiology might contribute to neurodegeneration in PD and ALS and could serve as a target for drug therapy.

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Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study

Cited by 90 publications

References 88 publications

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Navigated Transcranial Magnetic Stimulation Possibilities in Difficult Diagnostic Cases Upper Motor Neuron Lesions – Case Report

Mitochondrial Pathobiology in Parkinson's Disease and Amyotrophic Lateral Sclerosis

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