Neuroinflammation Induction and Alteration of Hippocampal Neurogenesis in Mice Following Developmental Exposure to Gossypol
| Autor: | Yongji Wu, Jian Huang, Xuejun Chai, Cixia Li, Enhui Cui, Xiaoyan Zhu, Ziluo Chen, Jiarong Pan, Shanting Zhao, Wentai Zhou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty cognitive deficits AcademicSubjects/MED00415 Neurogenesis Hippocampal formation Endocrine Disruptors Regular Research Articles Hippocampus neuroinflammation 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Pregnancy Internal medicine medicine Animals Pharmacology (medical) Cognitive Dysfunction Progenitor cell Pharmacology biology Behavior Animal AcademicSubjects/SCI01870 Dentate gyrus Gossypol hippocampal neurogenesis Brain development Neural stem cell Psychiatry and Mental health Disease Models Animal 030104 developmental biology Endocrinology chemistry Animals Newborn Prenatal Exposure Delayed Effects Neuroinflammatory Diseases biology.protein Female NeuN Neural development 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 1461-1457 |
| Popis: | Background Neurogenesis in the neonatal period involves the proliferation and differentiation of neuronal stem/progenitor cells and the establishment of synaptic connections. This process plays a critical role in determining the normal development and maturation of the brain throughout life. Exposure to certain physical or chemical factors during the perinatal period can lead to many neuropathological defects that cause high cognitive dysfunction and are accompanied by abnormal hippocampal neurogenesis and plasticity. As an endocrine disruptor, gossypol is generally known to exert detrimental effects in animals exposed under experimental conditions. However, it is unclear whether gossypol affects neurogenesis in the hippocampal dentate gyrus during early developmental stages. Methods Pregnant Institute of Cancer Research mice were treated with gossypol at a daily dose of 0, 20, and 50 mg/kg body weight from embryonic day 6.5 to postnatal day (P) 21. The changes of hippocampal neurogenesis as well as potential mechanisms were investigated by 5-bromo-2-deoxyuridine labeling, behavioral tests, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western-blot analyses. Results At P8, maternal gossypol exposure impaired neural stem cell proliferation in the dentate gyrus and decreased the number of newborn cells as a result of reduced proliferation of BLBP+ radial glial cells and Tbr2+ intermediate progenitor cells. At P21, the numbers of NeuN+ neurons and parvalbumin+ γ-aminobutyric acid-ergic interneurons were increased following 50 mg/kg gossypol exposure. In addition, gossypol induced hippocampal neuroinflammation, which may contribute to behavioral abnormalities and cognitive deficits and decrease synaptic plasticity. Conclusions Our findings suggest that developmental gossypol exposure affects hippocampal neurogenesis by targeting the proliferation and differentiation of neuronal stem/progenitor cells, cognitive functions, and neuroinflammation. The present data provide novel insights into the neurotoxic effects of gossypol on offspring. |
| Databáze: | OpenAIRE |
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