Dorsal CA3 overactivation mediates witnessing stress-induced recognition memory deficits in adolescent male mice
© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology..
Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology - (2024) vom: 19. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Xiao [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 20.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1038/s41386-024-01848-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369936167 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369936167 | ||
| 003 | DE-627 | ||
| 005 | 20240320235324.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240320s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41386-024-01848-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1337.xml |
| 035 | |a (DE-627)NLM369936167 | ||
| 035 | |a (NLM)38504012 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Xiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dorsal CA3 overactivation mediates witnessing stress-induced recognition memory deficits in adolescent male mice |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology. | ||
| 520 | |a Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ya-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hong-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Yu-Nu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xue-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Yun-Ai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ji-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Si, Tian-Mei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology |d 1988 |g (2024) vom: 19. März |w (DE-627)NLM012626821 |x 1740-634X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:19 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41386-024-01848-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 19 |c 03 | ||