Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors

Cunha, Andréia S.; Matheus, Filipe C.; Moretti, Morgana; Sampaio, Tuane Bazanella; Poli, Anicleto; Santos, Danúbia Bonfanti; Colle, Dirleise; Cunha, Maurício P.; Blum-Silva, Carlos H.; Sandjo, Louis P.; Reginatto, Flávio Henrique; Rodrigues, Ana Lúcia S.; Farina, Marcelo; Prediger, Rui Daniel

doi:10.1016/j.bbr.2016.06.014

Cited by 26 publications

(15 citation statements)

References 80 publications

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“…Studies have confirmed that eNOS plays a protective role in vascular injury. It can regulate vasodilation, improve microcirculation, and reduce the occurrence of thrombus [20,21]. After examining the levels of PDCD4, Akt, and eNOS, and activation status of the Akt signaling pathway, we found that PDCD4 gene silencing activated the Akt signaling pathway and promoted the expression of eNOS.…”

Section: Discussionmentioning

confidence: 99%

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

et al. 2019

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Background We aimed to investigate the role of PDCD4-mediated Akt signaling pathway in vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities. Material/Methods Ten rats were used as control, while 50 rats were used for creating disease models and were assigned to 5 groups: model group (no injection), NC group (injected with vectors containing PDCD negative control sequence), sh-PDCD4 group (injected with vectors containing sh-PDCD4 sequence), IGF-1 group (injected with IGF-1), and sh-PDCD4+IGF-1 group (injected with IGF-1 and vectors containing sh-PDCD4 sequence). Results Compared with the control group, the expression levels of PDCD4 mRNA and protein, as well as levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, increased in the other 5 groups, while the mRNA and protein expression levels of Akt and eNOS, the protein expression levels of p-Akt and p-eNOS, and superoxide dismutase content decreased in these groups (all P<0.05). Compared with the model group, the sh-PDCD4 and sh-PDCD4+1GF-1 groups had lower mRNA and protein expressions of PDCD4 (all P<0.05), whereas the IGF-1 group had similar levels (all P>0.05). These 3 groups had lower levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, and higher mRNA and protein expressions of Akt and eNOS, protein expressions of p-Akt and p-eNOS, and superoxide dismutase content (all P<0.05). The NC group did not differ from the model group (all P>0.05). Conclusions PDCD4 gene silencing can activate the Akt signaling pathway and attenuate vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities in rats.

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Section: Discussionmentioning

confidence: 99%

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

et al. 2019

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“…Since agmatine does not produce extrapyramidal side effects, it has been suggested that it might be a therapeutic target for schizophrenia treatment. In the literature there are some conflicting reports indicating the effect of agmatine and it has been discussed that the alterations in data might be due to the levels of endogenous agmatine [9,19,28,29]. Agmatine mainly metabolized by a specific enzyme, agmatinase, into different polyamines, which can bind and block glutamatergic NMDA receptors.…”

Section: Introductionmentioning

confidence: 99%

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Ünal

Ateş

Arıcıoğlu

2018

Psychiatry and Clinical Psychopharmacology

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INTRODUCTION: Schizophrenia is one of the most severe psychiatric disorders with about 1% prevalence. It has been proved that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists such as MK-801 and phencyclidine cause schizophrenia-like behaviours in rodents. Agmatine is an endogenous amine synthesized from decarboxylation of arginine and has been thought to be a neurotransmitter/neuromodulator. It binds to imidazoline and alfa adrenergic receptors and blocks cation channelled receptors, such as nicotinic acetylcholine, 5-HT3 serotonergic, and NMDA receptors. It is an endogenous inhibitor of nitric oxide synthase. A limited number of studies showed that agmatine attenuates sensorimotor gating deficit, which is an important parameter for schizophrenia, and improves cognitive deficits in rats. Despite this, it has also been shown that high doses of agmatine impaired sensorimotor gating. Herein, the aim of our study is to investigate the effect of subchronic agmatine treatment on sensorimotor gating, visual recognition memory, and social functions in subchronic MK-801 model of schizophrenia in rats. METHODS: Wistar Hannover rats were divided into four groups as control (dimethyl sulphoxide), MK-801 (0.2 mg/kg), MK-801 + agmatine (20 mg/kg), and MK-801 + risperidone (0.5 mg/kg)(n = 8 per group). MK-801 was subcutaneously injected once a day for 14 days. Agmatine and risperidone were administered intraperitoneally in the last seven days of MK-801 injections. On day 14, agmatine or risperidone was injected 15 minutes before MK-801 and MK-801 15 minutes before prepulse inhibition of the acoustic startle response (PPI) test. After the seven days washout period, social interaction (SI) test and novel object recognition test (NORT) were performed. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical evaluation of NORT, SI, and PPI, respectively. Paired Student's t-test was used for the comparison of rat's affinity to a familiar and novel object in NORT. RESULTS: MK-801 administration significantly decreased prepulse inhibition of rats in the PPI test (p < .001). In addition to this, MK-801 decreased startle response to pulse-alone trials and increased basal activity measured by the magnitude of no stimulus trials compared to the control group (p < .05). Agmatine treatment did not improve MK-801-induced PPI, startle response, or basal activity deficits while risperidone blocked the disruptive effect of MK-801 (p < .05). In NORT, the MK-801 group had significantly lower discrimination index (p < .05), whereas both the agmatine and risperidone treatments substantially increased this index (p < .01). Moreover, MK-801 injections not only decreased sniffing (p < .01) and following (p < .01) behaviours but also increased avoiding behaviour (p < .001) in SI. Agmatine partially treated social deficits (p < .001) while risperidone was reversed all of them (p < .01). CONCLUSIONS: Subchronic MK-801 administration revealed sensorimotor gating, social and cognitive deficits in rats. Subchroni...

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“…route with losartan (0.05–50 mg/kg) and/or istradefylline (0.03–0.06 mg/kg). VCM parameters were evaluated as previously described 81 but with some modifications. Thus, the evaluation of VCM frequency consists of a manual counting of continuous single mouth openings in a vertical plane, not directed to a physical material.…”

Section: Methodsmentioning

confidence: 99%

“…Mirrors were placed on the table and behind the glass cylinder (Ø 19 cm and 22 cm height) to allow observation of the orofacial movements when mice were not facing the observer. The evaluation of this parameter during 10 min was performed by a blind observer, 30 min after the pharmacological treatments administered 24 h after the second reserpine injection 81 .…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II type 1/adenosine A 2A receptor oligomers: a novel target for tardive dyskinesia

Oliveira

Dalton

López-Cano

et al. 2017

Sci Rep

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Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor heteromers. Here, we examined whether A2AR and AT1R may oligomerize in the striatum to synergistically modulate dopaminergic transmission. First, by using bioluminescence resonance energy transfer, we demonstrated a physical AT1R-A2AR interaction in cultured cells. Interestingly, by protein-protein docking and molecular dynamics simulations, we described that a stable heterotetrameric interaction may exist between AT1R and A2AR bound to antagonists (i.e. losartan and istradefylline, respectively). Accordingly, we subsequently ascertained the existence of AT1R/A2AR heteromers in the striatum by proximity ligation in situ assay. Finally, we took advantage of a TD animal model, namely the reserpine-induced vacuous chewing movement (VCM), to evaluate a novel multimodal pharmacological TD treatment approach based on targeting the AT1R/A2AR complex. Thus, reserpinized mice were co-treated with sub-effective losartan and istradefylline doses, which prompted a synergistic reduction in VCM. Overall, our results demonstrated the existence of striatal AT1R/A2AR oligomers with potential usefulness for the therapeutic management of TD.

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Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors

Cited by 26 publications

References 80 publications

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Angiotensin II type 1/adenosine A 2A receptor oligomers: a novel target for tardive dyskinesia

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