Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome
Abstract Fragile X syndrome (FXS) is caused by mutations in the fragile X mental retardation 1 gene, characterized by low plasma cholesterol levels. Considering the essential role of brain cholesterol in signaling and synaptogenesis, it is important to screen for brain cholesterol abnormalities in F...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227525000471 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849315981707444224 |
|---|---|
| author | Asma Laroui Daniela Rojas Sophie Bouhour Mélodie Proteau-Lemieux Luc Galarneau Sérine Benachenhou Armita Abolghasemi Rosalie Plantefeve Pierre-Luc Mallet François Corbin Jean-François Lepage Artuela Çaku |
| author_facet | Asma Laroui Daniela Rojas Sophie Bouhour Mélodie Proteau-Lemieux Luc Galarneau Sérine Benachenhou Armita Abolghasemi Rosalie Plantefeve Pierre-Luc Mallet François Corbin Jean-François Lepage Artuela Çaku |
| author_sort | Asma Laroui |
| collection | DOAJ |
| description | Abstract Fragile X syndrome (FXS) is caused by mutations in the fragile X mental retardation 1 gene, characterized by low plasma cholesterol levels. Considering the essential role of brain cholesterol in signaling and synaptogenesis, it is important to screen for brain cholesterol abnormalities in FXS and explore their link with neuropsychological profiles. Brain cholesterol is synthesized in situ, and the excess is primarily converted to 24(S)-hydroxycholesterol (24(S)-OHC). 27-hydroxycholesterol (27-OHC) is the major cholesterol oxidation metabolite that crosses the blood-brain barrier from peripheral circulation into the brain. Plasma levels of 24(S)-OHC and 27-OHC were quantified in FXS and control individuals. The FXS group underwent transcranial magnetic stimulation to evaluate corticospinal excitability and inhibition. The clinical profile was assessed using questionnaires evaluating specific symptoms related to autism, aberrant behaviors, and anxiety. Study results show a significant decrease in plasma levels of 24(S)-OHC in FXS as compared to controls (78.48 nM ± 20.90 vs. 99.53 nM ± 32.30; P = 0.006). Moreover, a negative correlation was observed between plasma levels of 24(S)-OHC and motor evoked potential (rs = −0.57; P = 0.05) in FXS. Similarly, a negative correlation was also found between plasma levels of 24(S)-OHC and the total score of the Social Communication Questionnaire (rs = −0.72; P = 0.002) and the Anxiety Depression and Mood Scale (rs = −0.61; P = 0.02). The 24(S)-OHC is associated with specific neurophysiological and behavioral characteristics in individuals with FXS. Larger studies are warranted to confirm the potential of 24(S)-OHC as a reliable biomarker for FXS. |
| format | Article |
| id | doaj-art-6819b25c5d644a2692d7e94c0c8ccb6c |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-6819b25c5d644a2692d7e94c0c8ccb6c2025-08-20T03:51:59ZengElsevierJournal of Lipid Research0022-22752025-05-0166510078710.1016/j.jlr.2025.100787Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndromeAsma Laroui0Daniela Rojas1Sophie Bouhour2Mélodie Proteau-Lemieux3Luc Galarneau4Sérine Benachenhou5Armita Abolghasemi6Rosalie Plantefeve7Pierre-Luc Mallet8François Corbin9Jean-François Lepage10Artuela Çaku11Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Psychology, University of Montreal, Montreal, Quebec, CanadaResearch Institute of the McGill University Health Centre, Montreal, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaDepartment of Paediatrics, Université de Sherbrooke, Sherbrooke, Quebec, Canada; For correspondence: Jean-François LepageDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Quebec, CanadaAbstract Fragile X syndrome (FXS) is caused by mutations in the fragile X mental retardation 1 gene, characterized by low plasma cholesterol levels. Considering the essential role of brain cholesterol in signaling and synaptogenesis, it is important to screen for brain cholesterol abnormalities in FXS and explore their link with neuropsychological profiles. Brain cholesterol is synthesized in situ, and the excess is primarily converted to 24(S)-hydroxycholesterol (24(S)-OHC). 27-hydroxycholesterol (27-OHC) is the major cholesterol oxidation metabolite that crosses the blood-brain barrier from peripheral circulation into the brain. Plasma levels of 24(S)-OHC and 27-OHC were quantified in FXS and control individuals. The FXS group underwent transcranial magnetic stimulation to evaluate corticospinal excitability and inhibition. The clinical profile was assessed using questionnaires evaluating specific symptoms related to autism, aberrant behaviors, and anxiety. Study results show a significant decrease in plasma levels of 24(S)-OHC in FXS as compared to controls (78.48 nM ± 20.90 vs. 99.53 nM ± 32.30; P = 0.006). Moreover, a negative correlation was observed between plasma levels of 24(S)-OHC and motor evoked potential (rs = −0.57; P = 0.05) in FXS. Similarly, a negative correlation was also found between plasma levels of 24(S)-OHC and the total score of the Social Communication Questionnaire (rs = −0.72; P = 0.002) and the Anxiety Depression and Mood Scale (rs = −0.61; P = 0.02). The 24(S)-OHC is associated with specific neurophysiological and behavioral characteristics in individuals with FXS. Larger studies are warranted to confirm the potential of 24(S)-OHC as a reliable biomarker for FXS.http://www.sciencedirect.com/science/article/pii/S0022227525000471fragile X messenger ribonucleoprotein 1cholesteroloxysterols24(S)-hydroxycholesterol27-hydroxycholesteroltranscranial magnetic stimulation |
| spellingShingle | Asma Laroui Daniela Rojas Sophie Bouhour Mélodie Proteau-Lemieux Luc Galarneau Sérine Benachenhou Armita Abolghasemi Rosalie Plantefeve Pierre-Luc Mallet François Corbin Jean-François Lepage Artuela Çaku Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome Journal of Lipid Research fragile X messenger ribonucleoprotein 1 cholesterol oxysterols 24(S)-hydroxycholesterol 27-hydroxycholesterol transcranial magnetic stimulation |
| title | Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome |
| title_full | Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome |
| title_fullStr | Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome |
| title_full_unstemmed | Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome |
| title_short | Associations between plasma 24(S)-hydroxycholesterol and neuropsychological profile in fragile X syndrome |
| title_sort | associations between plasma 24 s hydroxycholesterol and neuropsychological profile in fragile x syndrome |
| topic | fragile X messenger ribonucleoprotein 1 cholesterol oxysterols 24(S)-hydroxycholesterol 27-hydroxycholesterol transcranial magnetic stimulation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227525000471 |
| work_keys_str_mv | AT asmalaroui associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT danielarojas associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT sophiebouhour associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT melodieproteaulemieux associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT lucgalarneau associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT serinebenachenhou associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT armitaabolghasemi associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT rosalieplantefeve associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT pierrelucmallet associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT francoiscorbin associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT jeanfrancoislepage associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome AT artuelacaku associationsbetweenplasma24shydroxycholesterolandneuropsychologicalprofileinfragilexsyndrome |