Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1
Fragile-X syndrome (FXS) and Neurofibromatosis of type 1 (NF-1) are two monogenic disorders sharing neurobehavioral symptoms and pathophysiological mechanisms. Namely, preclinical models of both conditions show overactivity of the mTOR signaling pathway as well as GABAergic alterations. However, des...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612200273X |
| _version_ | 1811198289239867392 |
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| author | Angelina Lacroix Mélodie Proteau-Lemieux Samantha Côté Jamie Near Steve C.N. Hui Richard A.E. Edden Sarah Lippé Artuela Çaku François Corbin Jean-François Lepage |
| author_facet | Angelina Lacroix Mélodie Proteau-Lemieux Samantha Côté Jamie Near Steve C.N. Hui Richard A.E. Edden Sarah Lippé Artuela Çaku François Corbin Jean-François Lepage |
| author_sort | Angelina Lacroix |
| collection | DOAJ |
| description | Fragile-X syndrome (FXS) and Neurofibromatosis of type 1 (NF-1) are two monogenic disorders sharing neurobehavioral symptoms and pathophysiological mechanisms. Namely, preclinical models of both conditions show overactivity of the mTOR signaling pathway as well as GABAergic alterations. However, despite its potential clinical relevance for these disorders, the GABAergic system has not been systematically studied in humans. In the present study, we used an extensive transcranial magnetic stimulation (TMS) assessment battery in combination with magnetic resonance spectroscopy (MRS) to provide a comprehensive picture of the main inhibitory neurotransmitter system in patients with FXS and NF1. Forty-three participants took part in the TMS session (15 FXS, 10 NF1, 18 controls) and 36 in the MRS session (11 FXS, 14 NF1, 11 controls). Results show that, in comparison to healthy control participants, individuals with FXS and NF1 display lower GABA concentration levels as measured with MRS. TMS result show that FXS patients present increased GABAB-mediated inhibition compared to controls and NF1 patients, and that GABAA-mediated intracortical inhibition was associated with increased excitability specifically in the FXS groups. In line with previous reports, correlational analyses between MRS and TMS measures did not show significant relationships between GABA-related metrics, but several TMS measures correlated with glutamate+glutamine (Glx) levels assessed with MRS. Overall, these results suggest a partial overlap in neurophysiological alterations involving the GABA system in NF1 and FXS, and support the hypothesis that MRS and TMS assess different aspects of the neurotransmitter systems. |
| first_indexed | 2024-04-12T01:28:59Z |
| format | Article |
| id | doaj.art-dd05ea7cf2774bfebae823359cf4e7d0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-12T01:28:59Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-dd05ea7cf2774bfebae823359cf4e7d02022-12-22T03:53:33ZengElsevierNeurobiology of Disease1095-953X2022-11-01174105881Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1Angelina Lacroix0Mélodie Proteau-Lemieux1Samantha Côté2Jamie Near3Steve C.N. Hui4Richard A.E. Edden5Sarah Lippé6Artuela Çaku7François Corbin8Jean-François Lepage9Sherbrooke University Hospital Research Center, Sherbrooke, CanadaSherbrooke University Hospital Research Center, Sherbrooke, CanadaSherbrooke University Hospital Research Center, Sherbrooke, CanadaUniversity of Toronto, Medical Biophysics and Physical Sciences Platform at Sunnybrook Research Institute, Toronto, CanadaRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USARussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USADepartment of Psychology, Faculty of Arts and Sciences, Université de Montréal, Montréal, CanadaSherbrooke University Hospital Research Center, Sherbrooke, Canada; Department of Biochemistry, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, CanadaSherbrooke University Hospital Research Center, Sherbrooke, Canada; Department of Biochemistry, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, CanadaSherbrooke University Hospital Research Center, Sherbrooke, Canada; Departments of Pediatrics, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, Canada; Corresponding author at: Department of Pediatrics, Faculty of Medicine and Health Sciences, Sherbrooke University, 3001-12th Avenue North., Sherbrooke (Québec) J1H 5N4, Canada.Fragile-X syndrome (FXS) and Neurofibromatosis of type 1 (NF-1) are two monogenic disorders sharing neurobehavioral symptoms and pathophysiological mechanisms. Namely, preclinical models of both conditions show overactivity of the mTOR signaling pathway as well as GABAergic alterations. However, despite its potential clinical relevance for these disorders, the GABAergic system has not been systematically studied in humans. In the present study, we used an extensive transcranial magnetic stimulation (TMS) assessment battery in combination with magnetic resonance spectroscopy (MRS) to provide a comprehensive picture of the main inhibitory neurotransmitter system in patients with FXS and NF1. Forty-three participants took part in the TMS session (15 FXS, 10 NF1, 18 controls) and 36 in the MRS session (11 FXS, 14 NF1, 11 controls). Results show that, in comparison to healthy control participants, individuals with FXS and NF1 display lower GABA concentration levels as measured with MRS. TMS result show that FXS patients present increased GABAB-mediated inhibition compared to controls and NF1 patients, and that GABAA-mediated intracortical inhibition was associated with increased excitability specifically in the FXS groups. In line with previous reports, correlational analyses between MRS and TMS measures did not show significant relationships between GABA-related metrics, but several TMS measures correlated with glutamate+glutamine (Glx) levels assessed with MRS. Overall, these results suggest a partial overlap in neurophysiological alterations involving the GABA system in NF1 and FXS, and support the hypothesis that MRS and TMS assess different aspects of the neurotransmitter systems.http://www.sciencedirect.com/science/article/pii/S096999612200273XNeurodevelopmental disorderMRSTMSglutamatebrainERK |
| spellingShingle | Angelina Lacroix Mélodie Proteau-Lemieux Samantha Côté Jamie Near Steve C.N. Hui Richard A.E. Edden Sarah Lippé Artuela Çaku François Corbin Jean-François Lepage Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1 Neurobiology of Disease Neurodevelopmental disorder MRS TMS glutamate brain ERK |
| title | Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1 |
| title_full | Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1 |
| title_fullStr | Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1 |
| title_full_unstemmed | Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1 |
| title_short | Multimodal assessment of the GABA system in patients with fragile-X syndrome and neurofibromatosis of type 1 |
| title_sort | multimodal assessment of the gaba system in patients with fragile x syndrome and neurofibromatosis of type 1 |
| topic | Neurodevelopmental disorder MRS TMS glutamate brain ERK |
| url | http://www.sciencedirect.com/science/article/pii/S096999612200273X |
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