Cisplatin induces neuronal activation and increases central AMPA and NMDA receptor subunit gene expression in mice

Holland, Ruby A.; Leonard, John J.; Kensey, Nicholas A.; Hannikainen, Paavali A.; Jonghe, Bart C. De

doi:10.1016/j.physbeh.2014.02.038

Cited by 15 publications

(12 citation statements)

References 51 publications

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“…Induction of c-Fos within the NTS has previously been observed in cisplatin-induced nausea and vomiting in animals in accordance with the present findings. 9 17 34 Our study indicates that EA at both CV12 and PC6 may suppress the emetic response through inhibition of NTS activation.…”

Section: Discussionmentioning

confidence: 64%

“… 33 Regions of the central nervous system that are related to nausea and vomiting include the area postrema, NTS, vestibular system, amygdala, and insular cortex. 34 Among them, the NTS in the lower brainstem is the primary target site of vagal afferents and plays an important integrative role in the emetic response. Induction of c-Fos within the NTS has previously been observed in cisplatin-induced nausea and vomiting in animals in accordance with the present findings.…”

Section: Discussionmentioning

confidence: 99%

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Electroacupuncture Alleviates Cisplatin-Induced Nausea in Rats

et al. 2016

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ObjectiveAcupuncture has been shown to be effective for the treatment of chemotherapy-related nausea and vomiting. The aim of this study was to explore the mechanisms of action underlying the anti-emetic effect of electroacupuncture (EA).DesignForty-eight rats received saline (n=12) or 6 mg/kg cisplatin (n=36) to establish a chemotherapy-induced nausea and vomiting model. EA was performed at CV12 (n=12), bilateral PC6 (n=12), or sham points (n=12) 3 days before and 1–2 days after cisplatin administration (4–5 times in total), at 0.5–1 mA intensity and 2/15 Hz frequency for 10 min. Kaolin intake, food intake and bodyweight change were evaluated as markers of nausea and vomiting severity. Concentrations of serotonin (5-hydroxytryptamine, 5-HT) in the duodenum and c-Fos expression in the nucleus of the solitary tract (NTS) were measured using high performance liquid chromatography and immunohistochemistry, respectively.ResultsCisplatin administration led to increased kaolin intake and reduced food intake and bodyweight over the following 2 days. EA at CV12 significantly reversed the cisplatin-induced change in kaolin intake (on days 1 and 2) and food intake and bodyweight (on day 1). EA at CV12 also attenuated the cisplatin-induced increase in 5-HT in the duodenum and suppressed c-Fos expression in the NTS. EA at PC6 influenced kaolin intake (on day 1 only) and c-Fos expression, but had no statistically significant effect on food intake, bodyweight or 5-HT expression.ConclusionsThis study demonstrated beneficial effects of EA on chemotherapy-induced nausea and vomiting in a rat model. The anti-emetic effect of EA may be mediated through inhibition of 5-HT secretion in the duodenum and activity of the NTS.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Alleviates Cisplatin-Induced Nausea in Rats

et al. 2016

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“…In addition, as a known neurotoxic agent, cisplatin is suitable for use in NDD models, because it is known to cause memory and learning impairment through oxidative stress and neuroinflammation (Moneim, 2014; Oz et al, 2015; Zhou et al, 2016; Chen C. et al, 2017). Cisplatin modulates glutamate receptors and induces neural activation through the central upregulation of AMPARs and NMDARs (Holland et al, 2014). NMDARs antagonist protects against cisplatin-induced depression (Lehmann and Kärrberg, 1996).…”

Section: Glutamate Receptors As Potential Targets In Neurotoxic Agentmentioning

confidence: 99%

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Jakaria

Park

Haque

et al. 2018

Front. Mol. Neurosci.

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Glutamate receptors play a crucial role in the central nervous system and are implicated in different brain disorders. They play a significant role in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Although many studies on NDDs have been conducted, their exact pathophysiological characteristics are still not fully understood. In in vivo and in vitro models of neurotoxic-induced NDDs, neurotoxic agents are used to induce several neuronal injuries for the purpose of correlating them with the pathological characteristics of NDDs. Moreover, therapeutic drugs might be discovered based on the studies employing these models. In NDD models, different neurotoxic agents, namely, kainic acid, domoic acid, glutamate, β-N-Methylamino-L-alanine, amyloid beta, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, rotenone, 3-Nitropropionic acid and methamphetamine can potently impair both ionotropic and metabotropic glutamate receptors, leading to the progression of toxicity. Many other neurotoxic agents mainly affect the functions of ionotropic glutamate receptors. We discuss particular neurotoxic agents that can act upon glutamate receptors so as to effectively mimic NDDs. The correlation of neurotoxic agent-induced disease characteristics with glutamate receptors would aid the discovery and development of therapeutic drugs for NDDs.

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“…Cisplatin and other chemotherapeutic agents induce a mucosal injury of the intestines that includes serotonin-producing cells (33), and induce nausea and vomiting through signal transmission to the brain emetic center via the vagus nerve to abruptly release excessive 5-HT (34). Based on the results of the present and a previous study (12), EA at CV12 may affect 5-HT secretion in the duodenum and plasma, and deactivate neuronal transmission in the NTS, which may be evaluated through c-Fos protein expression as a metabolic marker of neuronal activation (35,36). These results suggest that acupuncture may exert an anti-emetic effect through regulating the secretion of the nausea-triggering peptide 5-HT and controlling the emetic center in the NTS through afferent vagal stimulation.…”

Section: Discussionmentioning

confidence: 65%

Electroacupuncture for chemotherapy‑induced anorexia through humoral appetite regulation: A preliminary experimental study

et al. 2019

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Chemotherapy-induced anorexia (CIA), which may lead to severe nutrition-associated problems, is a common complication associated with anti-cancer therapies. In the present study, the anti-anorexigenic effect of electroacupuncture (EA) was explored through assessing a change in appetite-associated peptides and c-Fos expression in a rat model of cisplatin-induced anorexia. In order to identify the most effective acupuncture point, 20 male Wistar rats (divided into five groups including the normal saline control, cisplatin only control and three groups according to the acupoints stimulated) were subjected to EA for 10 min at CV12, ST36 or PC6 daily for 4 days. Subsequently, the rats received intraperitoneal injections of cisplatin (6 mg/kg) to induce CIA. Food intake and reduction in body weight gain as the anorexia-associated outcomes were assessed daily for up to 3 days after cisplatin injection, and CV12 was eventually chosen as the most effective acupoint to test the anti-anorexigenic effect of EA. Furthermore, food intake, body weight and the concentrations of appetite-associated peptides, including ghrelin, cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT), in addition to c-Fos expression, were comparatively assessed between the CV12 EA group (n=6; rats treated with EA at CV12 daily for 4 days) and a control group (n=6; rats without treatment). The results indicated that the CV12 EA group exhibited a better outcome regarding food intake and body weight compared with the controls. Although there was no statistically significant difference observed, the secretion of serum ghrelin and CCK was increased in the CV12 EA group compared with that in the control group. The plasma level of 5-HT after cisplatin injection in the CV12 EA group was lower compared with that in the control, although no statistical significance was reached. Although not statistically significant, the expression of c-Fos protein in the nucleus tractus solitarius (NTS) was reduced in the CV12 EA rats. In addition, the hypothalamic mRNA levels of brain-derived neurotrophic factor (BDNF) were significantly increased in the CV12 EA group. In the hypothalamus, the expression of neuropeptide Y mRNA slightly increased in the cisplatin + CV12 EA group compared with the cisplatin only control group. In conclusion, the anti-anorexigenic effect of EA on CIA may be associated with an increase in the secretion of ghrelin and CCK and a decrease in the secretion of 5-HT into the serum, a reduction of c-Fos expression in the NTS and an increase in BDNF mRNA expression in the hypothalamus.

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Cisplatin induces neuronal activation and increases central AMPA and NMDA receptor subunit gene expression in mice

Cited by 15 publications

References 51 publications

Electroacupuncture Alleviates Cisplatin-Induced Nausea in Rats

Electroacupuncture Alleviates Cisplatin-Induced Nausea in Rats

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

Electroacupuncture for chemotherapy‑induced anorexia through humoral appetite regulation: A preliminary experimental study

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