Downregulation of GABAARα1 Aggravates Comorbidity of Epilepsy and Migraine via the TLR4 Signaling Pathway
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Experimental Grouping
2.2. Surgical Procedures
2.3. Establish LiCl-Pilocarpine Rat Epilepsy Model
2.4. Establish Migraine Model with Inflammatory Soup
2.5. Head-Scratching and Pain Threshold Recording
2.6. Drug Application
2.7. Western Blotting
2.8. Immunofluorescence Staining
2.9. Co-Immunoprecipitation
2.10. Statistical Analysis
3. Results
3.1. Changes in Behavioral Responses
3.2. Pilocarpine and Inflammatory Soup Disrupt TLR4 and GABAARα1 Expression Levels in Brain Tissue
3.3. Epilepsy–Migraine Comorbidity Leads to an Increase of Microglia
3.4. GABAARα1 Binds TLR4 and Regulates Its Expression
3.5. Activates GABAARα1 or Interferes with TLR4 Activity, Affecting Behavior in Comorbid Rats
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | |
---|---|---|---|---|---|
Control group (n = 6) | Surgery + PBS (I.P) (2:00 pm) | Saline (S.C) (08:00 am) PBS (I.P) (08:30 am) | PBS (08:30 am) | PBS (08:30 am) | PBS (08:30 am) |
Migraine group (n = 6) | Surgery PBS (I.P) | Saline (S.C) (08:00 am) PBS (I.P) (08:30 am) | IS (08:30 am) | IS (08:30 am) | IS (08:30 am) |
Epilepsy group (n = 6) | Surgery LiCl (I.P) | Atropine (S.C) (08:00 am) PILO (I.P) (08:30 am) | PBS (08:30 am) | PBS (08:30 am) | PBS (08:30 am) |
Comorbidity group (n = 6) | Surgery LiCl (I.P) | Atropine (S.C) (08:00 am) PILO (I.P) (08:30 am) | IS (08:30 am) | IS (08:30 am) | IS (08:30 am) |
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | |
---|---|---|---|---|---|
Comorbidity group (n = 3) | Surgery + LiCl (I.P) (2:00 pm) | DMSO) (07:00 am) + Sterile distilled water (08:00 am) (I.P) + PILO (I.P) (08:30 am) | DMSO (07:00 am) + Sterile distilled water (08:00 am) (I.P) + IS (08:30 am) | DMSO (07:00 am) + Sterile distilled water (08:00 am) (I.P) + IS (08:30 am) | DMSO (07:00 am) + Sterile distilled water (08:00 am) (I.P) + IS (08:30 am) |
Comorbidity +TAK-242 group (n = 3) | Surgery + LiCl (I.P) (2:00 pm) | TAK-242 (07:00 am) + Sterile distilled water (08:00 am) (I.P) + PILO (I.P) (08:30 am) | TAK-242 (07:00 am) + Sterile distilled water (08:00 am) (I.P) + IS (08:30 am) | TAK-242 (07:00 am) + Sterile distilled water (08:00 am) (I.P) + IS (08:30 am) | TAK-242 (07:00 am) + Sterile distilled water (08:00 am) (I.P) + IS (08:30 am) |
Comorbidity + Muscimol group (n = 3) | Surgery + LiCl (I.P) (2:00 pm) | DMSO (07:00 am) + Muscimol (08:00 am) (I.P) + PILO (I.P) (08:30 am) | DMSO (07:00 am) + Muscimol (08:00 am) (I.P) + IS (08:30 am) | DMSO (07:00 am) + Muscimol (08:00 am) (I.P) + IS (08:30 am) | DMSO (07:00 am) + Muscimol (08:00 am) (I.P) + IS (08:30 am) |
Control Group (n = 6) | Migraine Group (n = 6) | Epilepsy Group (n = 6) | Comorbidity Group (n = 6) | |
---|---|---|---|---|
the amount of head scratching | 66.33 ± 18.21 (times) | 135.50 ± 35.35 (times) | 41.83 ± 16.13 (times) | 207.67 ± 52.78 (times) |
facial mechanical withdrawal threshold (square root transformation) | 2.68 ± 0.63 (√g) | 1.23 ± 0.36 (√g) | 3.16 ± 0.55 (√g) | 0.75 ± 0.20 (√g) |
Epilepsy Group (n = 3) | Epilepsy + TAK-242 Group (n = 3) | Epilepsy + Muscimol Group (n = 3) | |
---|---|---|---|
The latency of epilepsy | 1338.0 ± 372.04 (s) | 1172.0 ± 244.83 (s) | 3083.0 ± 208.62 (s) |
Racine scale level of epilepsy | 4.67 ± 0.58 (level) | 4.33 ± 0.58 (level) | 3.33 ± 0.58 (level) |
Comorbidity Group (n = 3) | Comorbidity + TAK-242 Group (n = 3) | Comorbidity + Muscimol Group (n = 3) | |
---|---|---|---|
The amount of head scratching | 271.67 ± 23.46 (times) | 96.67 ± 23.71 (times) | 91.33 ± 11.15 (times) |
Facial mechanical withdrawal threshold (square root transformation) | 0.71 ± 0.14 (√g) | 3.07 ± 0.71 (√g) | 3.42 ± 0.78 (√g) |
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Lin, Y.; Ding, M.; Gong, Q.; Xiao, Z. Downregulation of GABAARα1 Aggravates Comorbidity of Epilepsy and Migraine via the TLR4 Signaling Pathway. Brain Sci. 2022, 12, 1436. https://doi.org/10.3390/brainsci12111436
Lin Y, Ding M, Gong Q, Xiao Z. Downregulation of GABAARα1 Aggravates Comorbidity of Epilepsy and Migraine via the TLR4 Signaling Pathway. Brain Sciences. 2022; 12(11):1436. https://doi.org/10.3390/brainsci12111436
Chicago/Turabian StyleLin, Yao, Man Ding, Qiaoyu Gong, and Zheman Xiao. 2022. "Downregulation of GABAARα1 Aggravates Comorbidity of Epilepsy and Migraine via the TLR4 Signaling Pathway" Brain Sciences 12, no. 11: 1436. https://doi.org/10.3390/brainsci12111436
APA StyleLin, Y., Ding, M., Gong, Q., & Xiao, Z. (2022). Downregulation of GABAARα1 Aggravates Comorbidity of Epilepsy and Migraine via the TLR4 Signaling Pathway. Brain Sciences, 12(11), 1436. https://doi.org/10.3390/brainsci12111436