Huntington's disease: biochemical prediction by determination of GABA synthesis of cultured fibroblasts

Göhlich, G.; Kühn, Wilfried; Höhn, H; Przuntek, H.

doi:10.1007/bf00313653

Cited by 7 publications

(3 citation statements)

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“…Indeed, a study identified a decreased expression of GAD67 in the prefrontal cortex of untreated MDD patients as compared to controls [ 143 ]. At last, GABA synthesis has been investigated in HDF to relate central impairment in Huntington disease context [ 144 ], and increased GABA neurotransmission has already been reported in the brain of a preclinical model of Huntington disease [ 145 ], suggesting that GABA metabolism impairment in HDF could reflect central dysfunctions.…”

Section: Resultsmentioning

confidence: 99%

Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response

Mesdom

Colle

Lebigot

et al. 2020

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Background: Human dermal fibroblasts (HDF) can be used as a cellular model relatively easily and without genetic engineering. Therefore, HDF represent an interesting tool to study several human diseases including psychiatric disorders. Despite major depressive disorder (MDD) being the second cause of disability in the world, the efficacy of antidepressant drug (AD) treatment is not sufficient and the underlying mechanisms of MDD and the mechanisms of action of AD are poorly understood. Objective: The aim of this review is to highlight the potential of HDF in the study of cellular mechanisms involved in MDD pathophysiology and in the action of AD response. Methods: The first part is a systematic review following PRISMA guidelines on the use of HDF in MDD research. The second part reports the mechanisms and molecules both present in HDF and relevant regarding MDD pathophysiology and AD mechanisms of action. Results: HDFs from MDD patients have been investigated in a relatively small number of works and most of them focused on the adrenergic pathway and metabolism-related gene expression as compared to HDF from healthy controls. The second part listed an important number of papers demonstrating the presence of many molecular processes in HDF, involved in MDD and AD mechanisms of action. Conclusion: The imbalance in the number of papers between the two parts highlights the great and still underused potential of HDF, which stands out as a very promising tool in our understanding of MDD and AD mechanisms of action.

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Section: Resultsmentioning

confidence: 99%

Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response

Mesdom

Colle

Lebigot

et al. 2020

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“…Human skin fibroblasts possess glutamate binding sites (Wong et al, 1984) and glutamate uptake sites (Comings et a]., 1981) and synthesize GABA (Gray and Dana, 1979;Hamel et al, 1981;Gohlich et al, 1984) by enzymatic conversion of L-glutamate via GAD. But up to now contradictory results were found regarding GABA synthesis in patients 0 1996 Rapid Science Publishers with HD compared to healthy controls, because Gray and Dana (1979) and Gohlich et al (1984) found a significant elevation of GAD activity in HD cells in contrast to Hamel et al (1981), who could not detect this difference. The method used by Hamel et al (1981) for measuring low GAD activity was too difficult and not suitable for large scale determinations.…”

Section: Introductionmentioning

confidence: 99%

Increased GABA synthesis in skin fibroblasts of patients with Huntington's disease: a possible role of glutamic acid decarboxylase?

Gerlach

Kühn

Müller

et al. 1996

Euro J of Neurology

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Activity of glutamic acid decarboxylase (GAD) was determined in extracts from cultured human skin fibroblasts of patients with Huntington's disease (HD) and compared to an age‐ and sex‐matched control group. The fibroblasts were cultured up to eight passages. In patients suffering from HD a significant increased activity of GAD (∼ 3–5 fold compared to age‐ and sex‐matched controls) was found in passages 4–8. This may indicate a defect in the genetic expression of GAD concentration or regulation and/or may indicate that increased levels of glutamate may also be responsible for neuronal degeneration in HD.

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“…Diese Befunde waren jedoch nicht reproduzierbar [4][5][6]. Auch die initial postulierten Veränderungen der Zellmembran von Fibroblasten oder eine erhöhte Gamma-Aminobuttersäure (GABA)-Synthese in kultivierten Fibroblasten ließen sich nicht bestätigen [7][8][9][10]. Im Bereich der Basalganglien, aber auch für den Kortex, wurden verschiedene Neurotransmitter-Veränderungen beschrieben.…”

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Fortschritte in Früh- und Verlaufsdiagnostik bei Morbus Huntington

Saft¹,

Kosinski²,

Landwehrmeyer³

2009

Akt Neurol

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Huntington's disease: biochemical prediction by determination of GABA synthesis of cultured fibroblasts

Cited by 7 publications

References 6 publications

Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response

Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response

Increased GABA synthesis in skin fibroblasts of patients with Huntington's disease: a possible role of glutamic acid decarboxylase?

Fortschritte in Früh- und Verlaufsdiagnostik bei Morbus Huntington

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