Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus
Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights m...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Behavioural Neurology |
| Online Access: | http://dx.doi.org/10.1155/2023/6991826 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832548026669858816 |
|---|---|
| author | Lijuan Chen Jing Li Xinglian Liu Zhiwei Zhao Yan Jin Yikun Fu Aiqin Zhou Chengqun Wang Yan Zhou |
| author_facet | Lijuan Chen Jing Li Xinglian Liu Zhiwei Zhao Yan Jin Yikun Fu Aiqin Zhou Chengqun Wang Yan Zhou |
| author_sort | Lijuan Chen |
| collection | DOAJ |
| description | Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus. |
| format | Article |
| id | doaj-art-f438f4bc82d64af9ab43f65efcd9f5cb |
| institution | Kabale University |
| issn | 1875-8584 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Behavioural Neurology |
| spelling | doaj-art-f438f4bc82d64af9ab43f65efcd9f5cb2025-02-03T06:42:44ZengWileyBehavioural Neurology1875-85842023-01-01202310.1155/2023/6991826Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the HippocampusLijuan Chen0Jing Li1Xinglian Liu2Zhiwei Zhao3Yan Jin4Yikun Fu5Aiqin Zhou6Chengqun Wang7Yan Zhou8Department of Pediatric NeurologyChildren’s Health DepartmentChildren’s Health DepartmentChildren’s Health DepartmentChildren’s Health DepartmentChildren’s Health DepartmentChildren’s Health DepartmentChildren’s Health DepartmentMass Spectrometry CenterVitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.http://dx.doi.org/10.1155/2023/6991826 |
| spellingShingle | Lijuan Chen Jing Li Xinglian Liu Zhiwei Zhao Yan Jin Yikun Fu Aiqin Zhou Chengqun Wang Yan Zhou Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus Behavioural Neurology |
| title | Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus |
| title_full | Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus |
| title_fullStr | Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus |
| title_full_unstemmed | Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus |
| title_short | Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus |
| title_sort | vitamin b6 deficiency induces autism like behaviors in rats by regulating mtor mediated autophagy in the hippocampus |
| url | http://dx.doi.org/10.1155/2023/6991826 |
| work_keys_str_mv | AT lijuanchen vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT jingli vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT xinglianliu vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT zhiweizhao vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT yanjin vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT yikunfu vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT aiqinzhou vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT chengqunwang vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus AT yanzhou vitaminb6deficiencyinducesautismlikebehaviorsinratsbyregulatingmtormediatedautophagyinthehippocampus |