Jieyu Anshen Granule, a Chinese Herbal Formulation, Exerts Effects on Poststroke Depression in Rats

Jieyu Anshen granule (JY) is a traditional Chinese medicine formula for treating depression and anxiety. The aim of the study was to observe the effects of JY on poststroke depression (PSD) and investigate the underlying mechanism. PSD rat model was developed by middle cerebral artery occlusion following chronic unpredictable mild stress in conjunction with isolation rearing. We performed behavioral tests, Western blot, ELISA, and BrdU/NeuN staining. Treatment with JY showed significant antidepressant effect in open-field and sucrose preference tests, as well as significant improvement in beam-walking, cylinder, grip strength, and water maze tests. In addition, treatment with JY could restore the levels of neurotransmitters and decrease the levels of hormone and inflammation cytokines in serum and brain. Treatment with JY also showed significant regulation in the expression of neurotransmitter receptors and NF-κB/IκB-α signaling in the prefrontal cortex and hippocampus. Moreover, the numbers of newborn neurons in the hippocampus were increased by treatment with JY. Our results suggest that JY could ameliorate PSD and improve the neurological and cognitive functions. The antidepressive effect may be associated with the modulation of JY on monoamine system, neuroendocrine, neuroinflammation, and neurogenesis.

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Xingnao Jieyu Decoction Ameliorates Poststroke Depression through the BDNF/ERK/CREB Pathway in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5403045 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Tao Li ◽

Dou Wang ◽

Bingbing Zhao ◽

Yongmei Yan

Keyword(s):

Hippocampal Neurons ◽

Artery Occlusion ◽

Immunofluorescence Assay ◽

Antidepressant Effect ◽

Tunel Staining ◽

Mild Stress ◽

Poststroke Depression ◽

Protein Levels ◽

Swimming Test ◽

Cerebral Artery Occlusion

Background.The neurotrophic pathway regulated by the brain-derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear.Objective.This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway.Methods.After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive-like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5-HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p-ERK/ERK, and p-CREB/CREB in the cortical and hippocampal regions were tested by Western blot.Results.The depressive-like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5-HT, NE, and BDNF and recovered the protein levels of p-ERK/ERK, p-CREB/CREB, and BDNF in the cortical and hippocampal regions.Conclusion.These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.

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Buyang Huanwu Decoction Ameliorates Poststroke Depression via Promoting Neurotrophic Pathway Mediated Neuroprotection and Neurogenesis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4072658 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Lin Luo ◽

Shuhua Deng ◽

Jian Yi ◽

Sainan Zhou ◽

Yan She ◽

...

Keyword(s):

Forced Swim Test ◽

Chronic Mild Stress ◽

Preference Test ◽

Underlying Mechanism ◽

Artery Occlusion ◽

Mild Stress ◽

Poststroke Depression ◽

Buyang Huanwu Decoction ◽

Sucrose Preference Test ◽

Cerebral Artery Occlusion

Objective.The aim of the present research is to investigate the therapeutic effect of Buyang Huanwu Decoction (BHD) in poststroke depression (PSD) animal model and illustrate its underlying mechanism via promoting neurotrophic pathway mediated neuroprotection and neurogenesis.Methods.To induce PSD rat model, isolation housed rats that received middle cerebral artery occlusion (MCAO) surgery successively suffered from chronic mild stress (CMS) treatment for consecutive twenty-one days. Meanwhile, rats were correspondingly given vehicle, BHD, and fluoxetine. Then, neurologic function was scored and depressive-like behaviors were assessed by sucrose preference test, locomotor activity, novelty-suppressed feeding test, and forced swim test. Thereafter, the neuroprotection and neurogenesis related molecular markers and signaling were detected.Results.We firstly observed a significant neurological function recovery and antidepressants effect of BHD after MCAO together with CMS treatment. Our study also found that treatment with BHD and fluoxetine can significantly rescue neurons from apoptosis and promote neurogenesis in the CA3 and DG regions in the hippocampus. Notably, BHD and fluoxetine treatment can activate BDNF/ERK/CREB signaling.Conclusion.The results suggest that BHD is a promising candidate for treating PSD. Its curative effects can be attributed to neurotrophic pathway mediated neuroprotection and neurogenesis.

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Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model

Neural Plasticity ◽

10.1155/2021/6635084 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Idriss Ali Abdoulaye ◽

Shan-shan Wu ◽

Enkhmurun Chibaatar ◽

Da-fan Yu ◽

Kai Le ◽

...

Keyword(s):

Synaptic Plasticity ◽

Dentate Gyrus ◽

Brain Regions ◽

Artery Occlusion ◽

Mild Stress ◽

Sprague Dawley ◽

Poststroke Depression ◽

Hippocampal Dentate Gyrus ◽

Downstream Signaling ◽

Antidepressant Effects

Background. Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods. To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results. Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-β and NMDAR2-α subtypes as well as their downstream signaling proteins β-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of β-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-β association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions. These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine’s lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.

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Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats

Neural Plasticity ◽

10.1155/2016/5054275 ◽

2016 ◽

Vol 2016 ◽

pp. 1-20

Author(s):

Jiro Kasahara ◽

Hiroto Uchida ◽

Kenta Tezuka ◽

Nanae Oka

Keyword(s):

Dentate Gyrus ◽

Neuronal Loss ◽

Immunohistochemical Analysis ◽

Granular Cell ◽

Artery Occlusion ◽

Poststroke Depression ◽

Hippocampal Dentate Gyrus ◽

Antidepressant Imipramine ◽

Effective Use ◽

Cerebral Artery Occlusion

Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min) operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine). The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.

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Bcl-2 enhances neurogenesis and inhibits apoptosis of newborn neurons in adult rat brain following a transient middle cerebral artery occlusion

Neurobiology of Disease ◽

10.1016/j.nbd.2006.07.012 ◽

2006 ◽

Vol 24 (2) ◽

pp. 345-356 ◽

Cited By ~ 66

Author(s):

Rong Zhang ◽

Yu-Yu Xue ◽

Shi-Duo Lu ◽

Yao Wang ◽

Ling-Mei Zhang ◽

...

Keyword(s):

Middle Cerebral Artery ◽

Rat Brain ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Artery Occlusion ◽

Adult Rat ◽

Adult Rat Brain ◽

Newborn Neurons ◽

Cerebral Artery Occlusion

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Beneficial Effects of Crocin against Depression via Pituitary Adenylate Cyclase-Activating Polypeptide

BioMed Research International ◽

10.1155/2020/3903125 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Linyu Lu ◽

Die Wu ◽

Kai Wang ◽

Juanjuan Tang ◽

Gang Chen

Keyword(s):

Adenylate Cyclase ◽

Pc12 Cells ◽

Neuroprotective Effect ◽

Preference Test ◽

Tail Suspension Test ◽

Adenosine Monophosphate ◽

Underlying Mechanism ◽

Antidepressant Effect ◽

Mild Stress ◽

Pituitary Adenylate Cyclase

Depression is one of the foremost psychological illness, and the exact mechanism is unclear. Recent studies have reported that the pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathway is involved in the progression of depression. In the present study, we extracted crocin from the traditional Chinese medicine (TCM), Gardenia jasminoides Ellis, to evaluate its antidepressant effect and clarify the underlying mechanism. Here, we established a chronic unpredictable mild stress (CUMS) mouse model to assess whether crocin can improve depression-like behavior in an open field test (OFT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT). A corticosterone (CORT) model of PC12 was set up to explore the antidepressant mechanism of crocin. We pretreated PC12 cells with crocin for 1 hour and then stimulated the cells with CORT for 24 hours. Cell survival was detected by Hoechst staining and MTT assay. The expression of PACAP, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and extracellular regulated protein kinases (ERK) were analyzed by western blotting. PACAP RNAi was used to interfere with PC12 cells to downregulate the content of PACAP. The results showed that crocin (30 mg/kg) significantly reversed the decrease of body weight and elevation of serum CORT, mitigated CUMS induced depression-like behaviors of mice, and crocin (12.5 μmol/L) protected PC12 cells against CORT (200 μmol/L)-induced injury. Furthermore, crocin greatly increased the protein expression of PACAP and phosphorylation of ERK and CREB in the CORT model. PACAP RNAi cancelled the neuroprotective effect of crocin. In conclusion, these results indicated that crocin exerted an antidepressant effect via upregulating PACAP and its downstream ERK and CREB signaling pathways.

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