Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress
Abstract Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
|
| Series: | Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-023-00406-4 |
| _version_ | 1797630181904482304 |
|---|---|
| author | Shilin Xu Keke Hao Ying Xiong Rui Xu Huan Huang Huiling Wang |
| author_facet | Shilin Xu Keke Hao Ying Xiong Rui Xu Huan Huang Huiling Wang |
| author_sort | Shilin Xu |
| collection | DOAJ |
| description | Abstract Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia. |
| first_indexed | 2024-03-11T11:03:25Z |
| format | Article |
| id | doaj.art-9f330ddc96014917a4138d7088db5297 |
| institution | Directory Open Access Journal |
| issn | 2754-6993 |
| language | English |
| last_indexed | 2024-03-11T11:03:25Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Schizophrenia |
| spelling | doaj.art-9f330ddc96014917a4138d7088db52972023-11-12T12:20:50ZengNature PortfolioSchizophrenia2754-69932023-11-019111210.1038/s41537-023-00406-4Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stressShilin Xu0Keke Hao1Ying Xiong2Rui Xu3Huan Huang4Huiling Wang5Department of Psychiatry, Renmin Hospital of Wuhan UniversityDepartment of Psychiatry, Renmin Hospital of Wuhan UniversityDepartment of Psychiatry, Renmin Hospital of Wuhan UniversityDepartment of Psychiatry, Renmin Hospital of Wuhan UniversityDepartment of Psychiatry, Renmin Hospital of Wuhan UniversityDepartment of Psychiatry, Renmin Hospital of Wuhan UniversityAbstract Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.https://doi.org/10.1038/s41537-023-00406-4 |
| spellingShingle | Shilin Xu Keke Hao Ying Xiong Rui Xu Huan Huang Huiling Wang Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress Schizophrenia |
| title | Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress |
| title_full | Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress |
| title_fullStr | Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress |
| title_full_unstemmed | Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress |
| title_short | Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress |
| title_sort | capsaicin alleviates neuronal apoptosis and schizophrenia like behavioral abnormalities induced by early life stress |
| url | https://doi.org/10.1038/s41537-023-00406-4 |
| work_keys_str_mv | AT shilinxu capsaicinalleviatesneuronalapoptosisandschizophrenialikebehavioralabnormalitiesinducedbyearlylifestress AT kekehao capsaicinalleviatesneuronalapoptosisandschizophrenialikebehavioralabnormalitiesinducedbyearlylifestress AT yingxiong capsaicinalleviatesneuronalapoptosisandschizophrenialikebehavioralabnormalitiesinducedbyearlylifestress AT ruixu capsaicinalleviatesneuronalapoptosisandschizophrenialikebehavioralabnormalitiesinducedbyearlylifestress AT huanhuang capsaicinalleviatesneuronalapoptosisandschizophrenialikebehavioralabnormalitiesinducedbyearlylifestress AT huilingwang capsaicinalleviatesneuronalapoptosisandschizophrenialikebehavioralabnormalitiesinducedbyearlylifestress |