TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis
Abstract Background Stroke is the major cause of adult neurocognitive disorders (NCDs), and presents a significant burden on both of the families and society. To improve the cerebral injury, we generated a blood–brain barrier penetrating peptide TAT‐LBD‐Ngn2, in which Ngn2 (Neurogenin2) is a classic...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Brain and Behavior |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/brb3.2847 |
| _version_ | 1797893710699036672 |
|---|---|
| author | Bin Feng Sansan Jia Liya Li Jiajia Wang Fang Zhou Xingchun Gou Qiang Wang Lize Xiong Yi Zeng Haixing Zhong |
| author_facet | Bin Feng Sansan Jia Liya Li Jiajia Wang Fang Zhou Xingchun Gou Qiang Wang Lize Xiong Yi Zeng Haixing Zhong |
| author_sort | Bin Feng |
| collection | DOAJ |
| description | Abstract Background Stroke is the major cause of adult neurocognitive disorders (NCDs), and presents a significant burden on both of the families and society. To improve the cerebral injury, we generated a blood–brain barrier penetrating peptide TAT‐LBD‐Ngn2, in which Ngn2 (Neurogenin2) is a classical preneural gene that enhances neurogenesis, and neural precursor cells survival and differentiation. We previously demonstrated that it has a short‐term protective effect against cerebral ischemia‐reperfusion injury. However, it is uncertain if TAT‐LBD‐Ngn2 could promote neurogenesis to exhibit long‐term therapeutic impact. Methods and results In present study, TAT‐LBD‐Ngn2 was administered for 14 or 28 days following bilateral common carotid arteries occlusion (BCCAO). After confirming that TAT‐LBD‐Ngn2 could cross the brain blood barrier and aggregate in the hippocampus, we conducted open field test, Morris water maze and contextual fear conditioning to examine the long‐term effect of TAT‐LBD‐Ngn2 on cognition. We discovered that TAT‐LBD‐Ngn2 significantly improved the spatial and contextual learning and memory on both days 14 and 28 after BCCAO, while TAT‐LBD‐Ngn2 exhibited anxiolytic effect only on day 14, but had no effect on locomotion. Using western blot and immunofluorescence, TAT‐LBD‐Ngn2 was also shown to promote neurogenesis, as evidenced by increased BrdU+ and DCX+ neurons in dentate gyrus. Meanwhile, TAT‐LBD‐Ngn2 elevated the expression of brain derived neurotrophic factor rather than nerve growth factor compared to the control group. Conclusions Our findings revealed that TAT‐LBD‐Ngn2 could dramatically promote learning and memory in long term by facilitating neurogenesis in the hippocampus after global cerebral ischemia, indicating that TAT‐LBD‐Ngn2 may be an appealing candidate for treating poststroke NCD. |
| first_indexed | 2024-04-10T06:57:15Z |
| format | Article |
| id | doaj.art-83ec2e9003e8442d984e782077938217 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-04-10T06:57:15Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-83ec2e9003e8442d984e7820779382172023-02-28T07:01:06ZengWileyBrain and Behavior2162-32792023-01-01131n/an/a10.1002/brb3.2847TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesisBin Feng0Sansan Jia1Liya Li2Jiajia Wang3Fang Zhou4Xingchun Gou5Qiang Wang6Lize Xiong7Yi Zeng8Haixing Zhong9Department of Radiation Oncology Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaShaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine Xi'an Medical University Xi'an ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Anesthesiology and perioperative medicine Xijing Hospital, The Fourth Military Medical University Xi'an Shaanxi ChinaAbstract Background Stroke is the major cause of adult neurocognitive disorders (NCDs), and presents a significant burden on both of the families and society. To improve the cerebral injury, we generated a blood–brain barrier penetrating peptide TAT‐LBD‐Ngn2, in which Ngn2 (Neurogenin2) is a classical preneural gene that enhances neurogenesis, and neural precursor cells survival and differentiation. We previously demonstrated that it has a short‐term protective effect against cerebral ischemia‐reperfusion injury. However, it is uncertain if TAT‐LBD‐Ngn2 could promote neurogenesis to exhibit long‐term therapeutic impact. Methods and results In present study, TAT‐LBD‐Ngn2 was administered for 14 or 28 days following bilateral common carotid arteries occlusion (BCCAO). After confirming that TAT‐LBD‐Ngn2 could cross the brain blood barrier and aggregate in the hippocampus, we conducted open field test, Morris water maze and contextual fear conditioning to examine the long‐term effect of TAT‐LBD‐Ngn2 on cognition. We discovered that TAT‐LBD‐Ngn2 significantly improved the spatial and contextual learning and memory on both days 14 and 28 after BCCAO, while TAT‐LBD‐Ngn2 exhibited anxiolytic effect only on day 14, but had no effect on locomotion. Using western blot and immunofluorescence, TAT‐LBD‐Ngn2 was also shown to promote neurogenesis, as evidenced by increased BrdU+ and DCX+ neurons in dentate gyrus. Meanwhile, TAT‐LBD‐Ngn2 elevated the expression of brain derived neurotrophic factor rather than nerve growth factor compared to the control group. Conclusions Our findings revealed that TAT‐LBD‐Ngn2 could dramatically promote learning and memory in long term by facilitating neurogenesis in the hippocampus after global cerebral ischemia, indicating that TAT‐LBD‐Ngn2 may be an appealing candidate for treating poststroke NCD.https://doi.org/10.1002/brb3.2847global cerebral ischemianeurogenesisneurogenin2post‐stroke neurocognitive disordersstroke |
| spellingShingle | Bin Feng Sansan Jia Liya Li Jiajia Wang Fang Zhou Xingchun Gou Qiang Wang Lize Xiong Yi Zeng Haixing Zhong TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis Brain and Behavior global cerebral ischemia neurogenesis neurogenin2 post‐stroke neurocognitive disorders stroke |
| title | TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis |
| title_full | TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis |
| title_fullStr | TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis |
| title_full_unstemmed | TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis |
| title_short | TAT‐LBD‐Ngn2‐improved cognitive functions after global cerebral ischemia by enhancing neurogenesis |
| title_sort | tat lbd ngn2 improved cognitive functions after global cerebral ischemia by enhancing neurogenesis |
| topic | global cerebral ischemia neurogenesis neurogenin2 post‐stroke neurocognitive disorders stroke |
| url | https://doi.org/10.1002/brb3.2847 |
| work_keys_str_mv | AT binfeng tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT sansanjia tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT liyali tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT jiajiawang tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT fangzhou tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT xingchungou tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT qiangwang tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT lizexiong tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT yizeng tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis AT haixingzhong tatlbdngn2improvedcognitivefunctionsafterglobalcerebralischemiabyenhancingneurogenesis |