Impact of indomethacin on neuroinflammation and hippocampal neurogenesis in aged mice

Boehme, Marcus; Guenther, Madlen; Stahr, Anna; Liebmann, Marie; Jaenisch, Nadine; Witte, Otto W.; Frahm, Christiane

doi:10.1016/j.neulet.2014.04.043

Cited by 32 publications

(28 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The activation of the inflammatory immune system may induce the decrease of neurons regeneration and neurotrophic factors release and enhancement of the neuroinflammation reaction [33, 34]. Microglia are the major innate immune cell population in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders, like depression, which are major cellular sources of TNF and IL-1 family of cytokines [35, 36]. Furthermore, several researches have reported that microglia cells in the brain were obviously activated in the brain of suicide victims [37], and antidepressants fluoxetine, paroxetine, and sertraline inhibited the microglial activation and reduced the release of inflammatory cytokines [38, 39].…”

Section: Discussionmentioning

confidence: 99%

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Zhong

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Neuroinflammation is considered as one of the common pathogeneses of depression. Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present study investigates the antidepressant-like effect of HJDT and its possible mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically), paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for 42 days. The depression-related behaviors, including sucrose preference test (SPT), open field test (OFT), novel objective recognition task (NORT), and forced swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA) contents, microglial activation, proinflammatory cytokines, and brain derived neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP-responsive element binding protein (CREB) expression were investigated. The results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression-like behaviors. Also HJDT decreased the number of microglia and the proinflammatory cytokines in hippocampus. Western-blotting analysis displayed HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus. Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But there was no difference in the 5-HT and DA contents with HJDT treatment. In conclusion, it was supposed that HJDT might be a potential Chinese medicine decoction for treating or alleviating complex symptoms of depression through BDNF-TrkB-CREB pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Zhong

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Indeed, there are inconsistencies in the literature regarding the effectiveness of indomethacin in reversing inflammation in the hippocampus. Although it has been shown to be effective in enhancing learning and memory by facilitating hippocampal synaptic transmission (see [86]), some studies have found that indomethacin is unable to effectively attenuate neuroinflammation and protect neurons in the hippocampus [87, 88]. The lack of effect of indomethacin on NOR performance could also stem from the 10-day gap between the last drug injection and NOR testing; in other words, it is possible that after the last administration the effects of indomethacin on recognition memory diminish over time and become undetectable at a certain point.…”

Section: Discussionmentioning

confidence: 99%

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

2017

View full text Add to dashboard Cite

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10–12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

show abstract

“…These molecules were detected within the VPA treatments at levels substantially below the non-treated ADSC controls. Higher expression levels of IL-1β [30,31], IL-6 [32] and TNF-α [33] are known to be inhibitory or to limit to neurogenesis as well as promote cellular proliferation. Chen et al, found that increased IL-1β limited neurogenesis by co-stimulation of STAT in the JAK/STAT pathway [34].…”

Section: Secreted Molecules Role In Signalling Pathways Controlling Nmentioning

confidence: 99%

Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways

Santos

Hubert

Milthorpe

2020

Cells

View full text Add to dashboard Cite

Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.

show abstract

Impact of indomethacin on neuroinflammation and hippocampal neurogenesis in aged mice

Cited by 32 publications

References 27 publications

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways

Contact Info

Product

Resources

About