Progesterone Neuroprotection in the Wobbler Mouse, a Genetic Model of Spinal Cord Motor Neuron Disease

Deniselle, Marı́a Claudia González; López‐Costa, Juan José; Saavedra, Jorge Pecci; Pietranera, Luciana; González, Susana; Garay, Laura; Guennoun, Rachida; Schumacher, Michaël; Nicola, Alejandro F. De

doi:10.1006/nbdi.2002.0564

Cited by 121 publications

(108 citation statements)

References 72 publications

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“…Morphological parameters of skin mitochondria were analyzed using a computerized image analyzer (OPTIMAS 6.02) 18 . Thus, quantitative analysis comprised determination of mitochondrial axis length, area, perimeter, size and the presence or absence of crystolysis, edema and membrane integrity.…”

Section: Electron Microscopymentioning

confidence: 99%

“…Muscle biopsies in SALS have shown increased mitochondrial volume associated to increased calcium levels 13 ; also, reduced activity of mitochondrial respiratory chain complex I and complex IV in skeletal muscle and the spinal cord have been reported 14,15 . Along this line, electron microscopy of motor neurons from animal models of ALS, including SOD1 transgenic and Wobbler mice, revealed prominent mitochondrial abnormalities, such as vacuolation, crystolysis, edema and rupture of outer membranes [16][17][18] .…”

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confidence: 99%

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Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

Rodríguez

González

Monachelli

et al. 2012

Arq. Neuro-Psiquiatr.

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OBJECTIVES: Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS). However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patients present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. METHODS: Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. RESULTS: Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. CONCLUSIONS: Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.

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Section: Electron Microscopymentioning

confidence: 99%

mentioning

confidence: 99%

Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

Rodríguez

González

Monachelli

et al. 2012

Arq. Neuro-Psiquiatr.

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“…In the rat spinal cord, progesterone (PROG) promotes neurological and functional recovery after contusion injury (Thomas et al, 1999) and promotes the survival of ventral motoneurons in the wobbler mouse, a genetic model of spinal cord motor disease (Gonzalez Deniselle et al, 2002). PROG also increases the survival of facial motoneurons after axotomy (Yu, 1989).…”

Section: Pleiotropic Effects Of Steroids In the Nervous System With Smentioning

confidence: 99%

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Schumacher

Weill-Engerer

Lière

et al. 2003

Progress in Neurobiology

272

171

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Without medical progress, dementing diseases such as Alzheimer's disease will become one of the main causes of disability. Preventing or delaying them has thus become a real challenge for biomedical research. Steroids offer interesting therapeutical opportunities for promoting successful aging because of their pleiotropic effects in the nervous system: they regulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination and influence cognitive processes, in particular learning and memory. Preclinical research has provided evidence that the normally aging nervous system maintains some capacity for regeneration and that age-dependent changes in the nervous system and cognitive dysfunctions can be reversed to some extent by the administration of steroids. The aging nervous system also remains sensitive to the neuroprotective effects of steroids. In contrast to the large number of studies documenting beneficial effects of steroids on the nervous system in young and aged animals, the results from hormone replacement studies in the elderly are so far not conclusive. There is also little information concerning changes of steroid levels in the aging human brain. As steroids present in nervous tissues originate from the endocrine glands (steroid hormones) and from local synthesis (neurosteroids), changes in blood levels of steroids with age do not necessarily reflect changes in their brain levels. There is indeed strong evidence that neurosteroids are also synthesized in human brain and peripheral nerves. The development of a very sensitive and precise method for the analysis of steroids by gas chromatography/mass spectrometry (GC/MS) offers new possibilities for the study of neurosteroids. The concentrations of a range of neurosteroids have recently been measured in various brain regions of aged Alzheimer's disease patients and aged non-demented controls by GC/MS, providing reference values. In Alzheimer's patients, there was a general trend toward lower levels of neurosteroids in different brain regions, and neurosteroid levels were negatively correlated with two biochemical markers of Alzheimer's disease, the phosphorylated tau protein and the ␤-amyloid peptides. The metabolism of dehydroepiandrosterone has also been analyzed for the first time in the aging brain from Alzheimer patients and non-demented controls. The conversion of dehydroepiandrosterone to 5-androstene-3␤,17␤-diol and to 7␣-OH-dehydroepiandrosterone occurred in frontal cortex, hippocampus, amygdala, cerebellum and striatum of both Alzheimer's patients and controls. The formation of these metabolites within distinct brain regions negatively correlated with the density of ␤-amyloid deposits.

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“…Some authors have suggested that a particular apoptosis occurs in SALS which has been named "cytoplasmic apoptosis", mainly consisting of cell shrinkage, cytoplasmatic blebbing, nuclear chromatin condensation and DNA degradation, conducted by the Ca++ activation of certain enzymes such as protein kinases, endonucleases, proteases and phospholipases 35 , which constitutes a different pathway from the one observed in the TgALS mode, in which the classical mitochondrial apoptotic pathway has been postulated. However, it is worth to note that in the Wobbler mice, neuronal death is accomplished by vacuolization of the motor neuron, instead of the classical apoptosis 36 .…”

Section: Sporadic Alsmentioning

confidence: 99%

Sporadic amyotrophic lateral sclerosis: new hypothesis regarding its etiology and pathogenesis suggests that astrocytes might be the primary target hosting a still unknown external agent

Sica¹,

Nicola²,

Deniselle³

et al. 2011

Arq. Neuro-Psiquiatr.

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This article briefly describes the already known clinical features and pathogenic mechanisms underlying sporadic amyotrophic lateral sclerosis, namely excitoxicity, oxidative stress, protein damage, inflammation, genetic abnormalities and neuronal death. Thereafter, it puts forward the hypothesis that astrocytes may be the cells which serve as targets for the harmful action of a still unknown environmental agent, while neuronal death may be a secondary event following the initial insult to glial cells. The article also suggests that an emergent virus or a misfolded infectious protein might be potential candidates to accomplish this task. Key words: ALS, SALS, pathogenesis, astrocytes.Esclerosis lateral amiotrófica esporádica: nueva hipótesis relacionada con su etiología y patogenia que sugiere que los astrocitos podrían ser el blanco primario alojando un agente nocivo aun desconocido RESUMEN El artículo presente describe, brevemente, las características clínicas y los mecanismos patogénicos de la esclerosis lateral amiotrófica esporádica, tales como la excitotoxicidad, el stress oxidativo, el daño proteico, la inflamación, las anormalidades genéticas y la muerte neuronal. Luego de ello, sugiere la posibilidad hipotética de que los astrocitos podrían ser el blanco primario de la acción de una agente ambiental, externo, aún desconocido, y que la muerte neuronal aconteciera secundariamente a ese daño astrocitario inicial. El artículo concluye discutiendo la posibilidad de que un virus ambiental o endógeno o una proteína mal plegada, que adquiriera características de infectividad, puedan ser la causa de la enfermedad. Palabras-clave: esclerosis lateral amiotrófica, esclerosis lateral amiotrófica esporádica, patogenia, astrocito.

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Progesterone Neuroprotection in the Wobbler Mouse, a Genetic Model of Spinal Cord Motor Neuron Disease

Cited by 121 publications

References 72 publications

Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Sporadic amyotrophic lateral sclerosis: new hypothesis regarding its etiology and pathogenesis suggests that astrocytes might be the primary target hosting a still unknown external agent

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