Vinča Institute of Nuclear Sciences, Laboratory for molecular biology and endocrinology, University of Belgrade, Serbia.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Psychiatry (UPK), University of Basel, Switzerland.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:386-399. doi: 10.1016/j.pnpbp.2018.10.013. Epub 2018 Oct 25.
Adult male rats exposed to chronic social isolation (CSIS) show depressive- and anxiety-like behaviors and reduce the numbers of parvalbumin-positive (PV+) interneurons in the dorsal hippocampus. We aimed to determine whether tianeptine (Tian), administered during the last three weeks of a six-week-social isolation (10 mg/kg/day), may reverse CSIS-induced behavioral changes and antagonize the CSIS-induced reduction in the number of PV+ interneurons. We also studied whether Tian affects the GABA-producing enzyme GAD67+ cells, in Stratum Oriens (SO), Stratum Pyramidale (SP), Stratum Radiatum (SR) and Stratum Lacunosum Moleculare (LM) of CA1-3, as well as in molecular layer-granule cell layer (ML-GCL) and Hilus (H) of the dentate gyrus (DG). CSIS-induced reduction in the number of PV+ cells was layer/subregion-specific with the greatest decrease in SO of CA2. Reduction in the number of PV+ cells was significantly higher than GAD67+ cells, indicating that PV+ cells are the main target following CSIS. Tian reversed CSIS-induced behavior phenotype and antagonized the reduction in the number of PV+ and GAD67+ cells in all subregions. In controls, Tian led to an increase in the number of PV+ and GAD67+ cells in SP of all subregions and PV+ interneurons in ML-GCL of DG, while treatment during CSIS, compared to CSIS alone, resulted with an increase of PV+ interneurons in SO and SP CA1, SP CA2/CA3 and ML-GCL DG with simultaneous increase in GAD67+ cells in all CA1, LM CA2, SO/SR/LM CA3. Data show that Tian offers protection from CSIS via modulation of the dorsal hippocampal GABAergic system.
成年雄性大鼠暴露于慢性社会隔离（CSIS）中会表现出抑郁和焦虑样行为，并减少背侧海马回中的钙结合蛋白阳性（PV+）中间神经元的数量。我们旨在确定在六周的社会隔离（10mg/kg/天）的最后三周给予噻奈普汀（Tian）是否可以逆转 CSIS 引起的行为变化，并拮抗 CSIS 引起的 PV+中间神经元数量减少。我们还研究了 Tian 是否会影响 GABA 产生酶 GAD67+细胞，包括 CA1-3 的 Stratum Oriens（SO）、Stratum Pyramidale（SP）、Stratum Radiatum（SR）和 Stratum Lacunosum Moleculare（LM），以及齿状回的分子层-颗粒细胞层（ML-GCL）和门区（H）。CSIS 诱导的 PV+细胞数量减少具有层/亚区特异性，CA2 的 SO 减少最为明显。PV+细胞数量的减少明显高于 GAD67+细胞，表明 PV+细胞是 CSIS 后的主要靶细胞。Tian 逆转了 CSIS 诱导的行为表型，并拮抗了所有亚区中 PV+和 GAD67+细胞数量的减少。在对照组中，Tian 导致所有亚区 SP 中的 PV+和 GAD67+细胞数量增加，以及 DG 的 ML-GCL 中的 PV+中间神经元数量增加，而在 CSIS 期间进行治疗与单独 CSIS 相比，导致 SO 和 SP CA1、SP CA2/CA3 和 ML-GCL DG 中的 PV+中间神经元增加，同时所有 CA1、LM CA2、SO/SR/LM CA3 中的 GAD67+细胞增加。数据表明，Tian 通过调节背侧海马回的 GABA 能系统提供对 CSIS 的保护。
