Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset
Abstract The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders. Chronic FLX treatment reportedly induces cellular responses in the brain, including increased adult hippocampal and cortical neurogenesis and reversal of neuron maturation i...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-08-01
|
| Series: | Molecular Brain |
| Online Access: | http://link.springer.com/article/10.1186/s13041-019-0489-5 |
| _version_ | 1818291855375204352 |
|---|---|
| author | Koji Ohira Hideo Hagihara Miki Miwa Katsuki Nakamura Tsuyoshi Miyakawa |
| author_facet | Koji Ohira Hideo Hagihara Miki Miwa Katsuki Nakamura Tsuyoshi Miyakawa |
| author_sort | Koji Ohira |
| collection | DOAJ |
| description | Abstract The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders. Chronic FLX treatment reportedly induces cellular responses in the brain, including increased adult hippocampal and cortical neurogenesis and reversal of neuron maturation in the hippocampus, amygdala, and cortex. However, because most previous studies have used rodent models, it remains unclear whether these FLX-induced changes occur in the primate brain. To evaluate the effects of FLX in the primate brain, we used immunohistological methods to assess neurogenesis and the expression of neuronal maturity markers following chronic FLX treatment (3 mg/kg/day for 4 weeks) in adult marmosets (n = 3 per group). We found increased expression of doublecortin and calretinin, markers of immature neurons, in the hippocampal dentate gyrus of FLX-treated marmosets. Further, FLX treatment reduced parvalbumin expression and the number of neurons with perineuronal nets, which indicate mature fast-spiking interneurons, in the hippocampus, but not in the amygdala or cerebral cortex. We also found that FLX treatment increased the generation of cortical interneurons; however, significant up-regulation of adult hippocampal neurogenesis was not observed in FLX-treated marmosets. These results suggest that dematuration of hippocampal neurons and increased cortical neurogenesis may play roles in FLX-induced effects and/or side effects. Our results are consistent with those of previous studies showing hippocampal dematuration and increased cortical neurogenesis in FLX-treated rodents. In contrast, FLX did not affect hippocampal neurogenesis or dematuration of interneurons in the amygdala and cerebral cortex. |
| first_indexed | 2024-12-13T02:50:42Z |
| format | Article |
| id | doaj.art-e232f729694340f5b197eb5d287f33cb |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-13T02:50:42Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-e232f729694340f5b197eb5d287f33cb2022-12-22T00:02:04ZengBMCMolecular Brain1756-66062019-08-0112111010.1186/s13041-019-0489-5Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmosetKoji Ohira0Hideo Hagihara1Miki Miwa2Katsuki Nakamura3Tsuyoshi Miyakawa4Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health UniversityDivision of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health UniversityCognitive Neuroscience Section, Primate Research Institute, Kyoto UniversityCognitive Neuroscience Section, Primate Research Institute, Kyoto UniversityDivision of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health UniversityAbstract The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders. Chronic FLX treatment reportedly induces cellular responses in the brain, including increased adult hippocampal and cortical neurogenesis and reversal of neuron maturation in the hippocampus, amygdala, and cortex. However, because most previous studies have used rodent models, it remains unclear whether these FLX-induced changes occur in the primate brain. To evaluate the effects of FLX in the primate brain, we used immunohistological methods to assess neurogenesis and the expression of neuronal maturity markers following chronic FLX treatment (3 mg/kg/day for 4 weeks) in adult marmosets (n = 3 per group). We found increased expression of doublecortin and calretinin, markers of immature neurons, in the hippocampal dentate gyrus of FLX-treated marmosets. Further, FLX treatment reduced parvalbumin expression and the number of neurons with perineuronal nets, which indicate mature fast-spiking interneurons, in the hippocampus, but not in the amygdala or cerebral cortex. We also found that FLX treatment increased the generation of cortical interneurons; however, significant up-regulation of adult hippocampal neurogenesis was not observed in FLX-treated marmosets. These results suggest that dematuration of hippocampal neurons and increased cortical neurogenesis may play roles in FLX-induced effects and/or side effects. Our results are consistent with those of previous studies showing hippocampal dematuration and increased cortical neurogenesis in FLX-treated rodents. In contrast, FLX did not affect hippocampal neurogenesis or dematuration of interneurons in the amygdala and cerebral cortex.http://link.springer.com/article/10.1186/s13041-019-0489-5 |
| spellingShingle | Koji Ohira Hideo Hagihara Miki Miwa Katsuki Nakamura Tsuyoshi Miyakawa Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset Molecular Brain |
| title | Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset |
| title_full | Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset |
| title_fullStr | Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset |
| title_full_unstemmed | Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset |
| title_short | Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset |
| title_sort | fluoxetine induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset |
| url | http://link.springer.com/article/10.1186/s13041-019-0489-5 |
| work_keys_str_mv | AT kojiohira fluoxetineinduceddematurationofhippocampalneuronsandadultcorticalneurogenesisinthecommonmarmoset AT hideohagihara fluoxetineinduceddematurationofhippocampalneuronsandadultcorticalneurogenesisinthecommonmarmoset AT mikimiwa fluoxetineinduceddematurationofhippocampalneuronsandadultcorticalneurogenesisinthecommonmarmoset AT katsukinakamura fluoxetineinduceddematurationofhippocampalneuronsandadultcorticalneurogenesisinthecommonmarmoset AT tsuyoshimiyakawa fluoxetineinduceddematurationofhippocampalneuronsandadultcorticalneurogenesisinthecommonmarmoset |