Anti-depressant-like effects of Jieyu chufan capsules in a mouse model of unpredictable chronic mild stress

Abstract

Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups). The MC group and the three JYCF groups were subjected to 3 weeks of unpredictable chronic mild stress (UCMS) to induce depression-like behavior. All groups were subjected to a sucrose consumption test along with a forced swimming test to confirm depression-like behavior, an open-field test and an elevated plus maze test to confirm anxiety-like behavior, and a Morris water maze test to evaluate spatial learning and memory. In addition, synaptic density in the hippocampus was evaluated and western blot and immunostaining were used to analyze hippocampal expression of postsynaptic density protein-95 (PSD95), synaptophysin (Syn), cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt and glycogen synthase kinase (GSK)-3β as well as their phosphorylated (p) versions. The results showed that JYCF (2.5 and 5 g/kg) alleviated depressive-like behaviors and increased synaptic density in UCMS mice. Moreover, JYCF upregulated the expression of PSD95, Syn and BDNF and increased phosphorylated Akt, CREB and GSK-3β in the hippocampus. These results suggested that JYCF exerts an anti-depressant-like activity in UCMS-induced mice, which is likely to be mediated by reversing the stress-induced disruption of BDNF and GSK-3β activity.

Efeitos comportamentais e neuroplásticos da combinação de escitalopram e canabinóides

“…Por outro lado, cronicamente, haveria uma dessensibilização desses autorreceptores e, dessa forma, o aumento da disponibilidade de 5-HT seria muito mais marcante. FASS et al, 2014;MATTSON et al, 2018;TARDITO et al, 2006 As manifestações neuroplásticas maladaptativas descritas em condições de estresse crônico em modelos animais incluem atrofia da arborização dendrítica e redução do número de espinhos dendríticos de neurônios piramidais da região CA3 e de neurônios piramidais das camadas II e III do córtex pré-frontal medial (CHEN et al, 2008;COOK;WELLMAN, 2004;HAINS et al, 2009;MAGARIÑOS et al, 1996;MAGARIÑOS;MCEWEN, 1995;RADLEY et al, 2006;WATANABE;GOULD;MCEWEN, 1992), prejuízo na indução de potenciação de longo prazo (long-term potentiation, LTP) na via perforante, nos colaterais de Schaffer e na via hipocampocórtex pré-frontal (CERQUEIRA et al, 2007;FOY et al, 1987;KIM;FOY;THOMPSON, 1996;MCEWEN, 1999;DRYVER, 1994;SERVATIUS, 1995), facilitação do fenômeno de depressão de longo prazo (long-term depression, LTD) nos colaterais de Schaffer (KIM; FOY; THOMPSON, 1996), redução nos níveis de fatores neurotróficos como BDNF (HASHIKAWA et al, 2015;THAKARE et al, 2017;VAN BOXELAERE et al, 2017;ZU et al, 2017), diminuição na expressão de proteínas de estabilidade sináptica, como PSD95 (ZHAO et al, 2017), alterações na maquinaria de liberação de neurotransmissores (MÜLLER et al, 2011;THOME et al, 2001;ZHAO et al, 2017), alteração na expressão e função de receptores, incluindo receptores glutamatérgicos AMPA e NMDA (WEI et al, 2016;…”