Activation of the 5-HT7 receptor and MMP-9 signaling module in the hippocampal CA1 region is necessary for the development of depressive-like behavior

被引：35

作者：

Bijata, Monika ^{[1
,2
]}

Baczynska, Ewa ^{[1
,3
]}

Mueller, Franziska E. ^{[2
]}

Bijata, Krystian ^{[1
,4
]}

Masternak, Julia ^{[1
]}

Krzystyniak, Adam ^{[1
]}

Szewczyk, Bernadeta ^{[5
]}

Siwiec, Marcin ^{[6
]}

Antoniuk, Svitlana ^{[1
,2
]}

Roszkowska, Matylda ^{[1
]}

Figiel, Izabela ^{[1
]}

Magnowska, Marta ^{[1
]}

Olszynski, Krzysztof H. ^{[8
]}

Wardak, Agnieszka D. ^{[8
]}

Hogendorf, Adam ^{[7
]}

Ruszczycki, Blazej ^{[1
]}

Gorinski, Nataliya ^{[2
]}

Labus, Josephine ^{[2
]}

Stepien, Tomasz ^{[9
]}

Tarka, Sylwia ^{[10
]}

Bojarski, Andrzej J. ^{[7
]}

Tokarski, Krzysztof ^{[6
]}

Filipkowski, Robert K. ^{[8
]}

Ponimaskin, Evgeni ^{[2
]}

Wlodarczyk, Jakub ^{[1
]}

机构：

[1] Polish Acad Sci, Nencki Inst Expt Biol, Pasteura 3, PL-02093 Warsaw, Poland

[2] Hannover Med Sch, Ctr Physiol, Cellular Neurophysiol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[3] Polish Acad Sci, Inst Phys Chem, Kasprzaka 44-52, PL-01224 Warsaw, Poland

[4] Univ Warsaw, Fac Chem, Pasteura 1, PL-02093 Warsaw, Poland

[5] Polish Acad Sci, Maj Inst Pharmacol, Dept Neurobiol, Smetna 12, PL-31343 Krakow, Poland

[6] Polish Acad Sci, Maj Inst Pharmacol, Dept Physiol, Smetna 12, PL-31343 Krakow, Poland

[7] Polish Acad Sci, Maj Inst Pharmacol, Dept Med Chem, Smetna 12, PL-31343 Krakow, Poland

[8] Polish Acad Sci, Mossakowski Med Res Inst, Behav & Metab Res Lab, Pawinskiego 5, PL-02106 Warsaw, Poland

[9] Inst Psychiat & Neurol, Dept Neuropathol, Jana III Sobieskiego 9, PL-02957 Warsaw, Poland

[10] Med Univ Warsaw, Dept Forens Med, Oczki 1, PL-02007 Warsaw, Poland

来源：

CELL REPORTS | 2022年 / 38卷 / 11期

关键词：

LONG-TERM POTENTIATION; MATRIX-METALLOPROTEINASE-9; MMP-9; MICROGLIAL ACTIVATION; ANTAGONIST SB-269970; DENDRITIC FILOPODIA; SYNAPTIC PLASTICITY; SEROTONIN RECEPTORS; PLASMA-LEVELS; STRESS; BRAIN;

D O I：

10.1016/j.celrep.2022.110532

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Major depressive disorder is a complex disease resulting from aberrant synaptic plasticity that may be caused by abnormal serotonergic signaling. Using a combination of behavioral, biochemical, and imaging methods, we analyze 5-HT7R/MMP-9 signaling and dendritic spine plasticity in the hippocampus in mice treated with the selective 5-HT7R agonist (LP-211) and in a model of chronic unpredictable stress (CUS)induced depressive-like behavior. We show that acute 5-HT7R activation induces depressive-like behavior in mice in an MMP-9-dependent manner and that post mortem brain samples from human individuals with depression reveal increased MMP-9 enzymatic activity in the hippocampus. Both pharmacological activation of 5-HT7R and modulation of its downstream effectors as a result of CUS lead to dendritic spine elongation and decreased spine density in this region. Overall, the 5-HT7R/MMP-9 pathway is specifically activated in the CA1 subregion of the hippocampus during chronic stress and is crucial for inducing depressive-like behavior.

引用

页数：23

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