Tyrosine hydroxylase deficit in the chemoafferent and the sympathoadrenergic pathways of the Mecp2 deficient mouse

Roux, Jean‐Christophe; Dura, Emmanuelle; Villard, Laurent

doi:10.1016/j.neulet.2008.09.045

Cited by 45 publications

(45 citation statements)

References 40 publications

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“…A catecholaminergic deficit has been also observed in the sympathoadrenergic and the chemoafferent pathway of Mecp2-deficient mice (Wang et al 2006;Roux et al 2008;Ladas et al 2009). Because the chemoafferent pathway is directly involved in the regulation of the cardiorespiratory system during hypoxic stimulation, such deficits could explain the inappropriate ventilatory response measured using Mecp2-deficient mouse models Bissonnette and Knopp 2008).…”

Section: Defects Of Biogenic Amines In Mouse Models Of Rett Syndromementioning

confidence: 95%

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Biogenic Amines in Rett Syndrome: The Usual Suspects

Roux

Villard

2009

Behav Genet

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Rett syndrome (RTT) is a severe postnatal neurological disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. In affected children, most biological parameters, including brain structure, are normal (although acquired microcephaly is usually present). However, in recent years, a deficit in bioaminergic metabolism has been identified at the cellular and molecular levels, in more than 200 patients. Recently available transgenic mouse strains with a defective Mecp2 gene also show abnormalities, strongly suggesting that there is a direct link between the function of the MECP2 protein and the metabolism of biogenic amines. Biogenic amines appear to have an important role in the pathophysiology of Rett syndrome, for several reasons. Firstly, biogenic amines modulate a large number of autonomic and cognitive functions. Secondly, many of these functions are affected in RTT patients. Thirdly, biogenic amines are the only neurotransmitters that have repeatedly been found to be altered in RTT patients. Importantly, pharmacological interventions can be envisaged to try to counteract the deficits observed. Here, we review the available human and mouse data and present how they have been and could be used in the development of pharmacological treatments for children affected by the syndrome. Given our current knowledge and the tools available, modulating biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of Rett syndrome patients in the short term.

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Section: Defects Of Biogenic Amines In Mouse Models Of Rett Syndromementioning

confidence: 95%

“…et al (2005),Roux et al (2008),Bissonnette and Knopp (2008),Voituron et al (2009) a This work was performed using a human SH-SY5Y neuroblastoma cell line…”

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confidence: 99%

Biogenic Amines in Rett Syndrome: The Usual Suspects

Roux

Villard

2009

Behav Genet

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“…Multiple studies have documented low levels of neurotransmitters (dopamine, 5-HT, noradrenaline) in autopsy RTT brains and in MECP2-deficient mice [152]. Desipramine, an antidepressant that blocks the uptake of noradrenaline and has been shown to reverse the depletion of tyrosine hydroxylase in the brainstem, helps the regulation of breathing and extending the life span of male MECP2 knockout mice [153].…”

Section: Neurotransmittersmentioning

confidence: 99%

Intracellular Pathways Associated with the Etiology of Autism

Russo¹

2017

Autism - Paradigms, Recent Research and Clinical Applications

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This chapter explores the relationship between the genes and proteins of the Akt and MAPK pathways and autism. This chapter presents the biology of these two pathways, their genes and cascading proteins, and then, it looks at the research that has connected these molecules to autism. Finally, it imparts current and future therapeutic modalities that might exploit abnormalities in these genes and proteins, change them and ultimately alter aberrant autistic behaviors.

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“…Neurotransmitter Systems: Monoamines, Glutamate and γ-Aminobutyric Acid Monoamine neurotransmitters like dopamine, serotonin, and noradrenaline have been found to be reduced in autopsy of RTT brains and in Mecp2-deficient mice [97][98][99][100]. As these monoamines are associated with the regulation of breathing patterns in the brainstem, augmenting their levels may be therapeutic for breathing dysfunction in RTT.…”

Section: Neurotrophins and Growth Factors: Brain-derived Neurotrophicmentioning

confidence: 99%

Rett Syndrome: Reaching for Clinical Trials

2015

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Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT.

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Tyrosine hydroxylase deficit in the chemoafferent and the sympathoadrenergic pathways of the Mecp2 deficient mouse

Cited by 45 publications

References 40 publications

Biogenic Amines in Rett Syndrome: The Usual Suspects

Biogenic Amines in Rett Syndrome: The Usual Suspects

Intracellular Pathways Associated with the Etiology of Autism

Rett Syndrome: Reaching for Clinical Trials

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