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High dosage of agmatine alleviates pentylenetetrazole-induced chronic seizures in rats possibly by exerting an anticonvulsive effect.

Xu H, Ou F, Wang P, Naren M, Tu D, Zheng R - Exp Ther Med (2014)

Bottom Line: The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area.Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus.Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.

ABSTRACT
The aim of the present study was to investigate the mechanism underlying the effects of different doses of agmatine in rats with chronic epilepsy. To generate chronic epilepsy models, rats pretreated with different doses of agmatine (20, 40 and 80 mg/kg) were intraperitoneally injected with pentylenetetrazole (35 mg/kg) for 28 consecutive days. Epileptic behavior was observed using behavioral measurements of convulsion for 1 h after each treatment with pentylenetetrazole. Morphological alterations of the hippocampal neurons were also observed using hematoxylin and eosin staining. In addition, the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus were detected by immunohistochemistry. Furthermore, reverse transcription polymerase chain reaction was performed to detect the mRNA expression of two subunits (NR1 and NR2B) of the N-methyl-D-aspartic acid (NMDA) receptor in the rat hippocampus. The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area. Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus. Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Our results suggest that agmatine has an anticonvulsive effect in chronic epilepsy.

No MeSH data available.


Related in: MedlinePlus

(A) Detection of NMDAR1 mRNA expression in the rat hippocampus using reverse transcription polymerase chain reaction. A, normal control group; B, model control group; C1, C2 and C3, agmatine groups (20, 40 and 80 mg/kg, respectively). (B) Quantification of NMDAR1 mRNA expression of the five groups. The Y axis indicates the ratio of optical density (OD) of the samples to the corresponding internal standard (β-actin). Data are expressed as the mean ± standard error of the mean (n=10). *P<0.05, **P<0.01, compared with the normal control group. ΔP<0.01, for comparisons between the agmatine group and the model control group. NMDAR1, N-methyl-D-aspartic acid receptor; AGM, agmatine; PTZ, pentylenetetrazole.
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f4-etm-08-01-0073: (A) Detection of NMDAR1 mRNA expression in the rat hippocampus using reverse transcription polymerase chain reaction. A, normal control group; B, model control group; C1, C2 and C3, agmatine groups (20, 40 and 80 mg/kg, respectively). (B) Quantification of NMDAR1 mRNA expression of the five groups. The Y axis indicates the ratio of optical density (OD) of the samples to the corresponding internal standard (β-actin). Data are expressed as the mean ± standard error of the mean (n=10). *P<0.05, **P<0.01, compared with the normal control group. ΔP<0.01, for comparisons between the agmatine group and the model control group. NMDAR1, N-methyl-D-aspartic acid receptor; AGM, agmatine; PTZ, pentylenetetrazole.

Mentions: In order to analyze the alterations in the expression of the NMDA receptor induced by agmatine, RT-PCR was performed to detect NR1 and NR2b mRNA expression in the rat hippocampus (Fig. 4A). Compared with the model control group, the quantity of NR1 mRNA in the agmatine groups (40 and 80 mg/kg) was significantly decreased (P<0.01), suggesting that pretreatment with agmatine may suppress the actions of the hippocampal NR1 (Fig. 4B). However, the low-dose agmatine group (20 mg/kg) showed no significant difference compared with the model control group (Fig. 4B). In addition, no significant difference in NR2b mRNA expression was observed among all the groups (data not shown). These results indicated that treatment with higher concentrations of agmatine decreased the expression of the NMDA receptor.


High dosage of agmatine alleviates pentylenetetrazole-induced chronic seizures in rats possibly by exerting an anticonvulsive effect.

Xu H, Ou F, Wang P, Naren M, Tu D, Zheng R - Exp Ther Med (2014)

(A) Detection of NMDAR1 mRNA expression in the rat hippocampus using reverse transcription polymerase chain reaction. A, normal control group; B, model control group; C1, C2 and C3, agmatine groups (20, 40 and 80 mg/kg, respectively). (B) Quantification of NMDAR1 mRNA expression of the five groups. The Y axis indicates the ratio of optical density (OD) of the samples to the corresponding internal standard (β-actin). Data are expressed as the mean ± standard error of the mean (n=10). *P<0.05, **P<0.01, compared with the normal control group. ΔP<0.01, for comparisons between the agmatine group and the model control group. NMDAR1, N-methyl-D-aspartic acid receptor; AGM, agmatine; PTZ, pentylenetetrazole.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061208&req=5

f4-etm-08-01-0073: (A) Detection of NMDAR1 mRNA expression in the rat hippocampus using reverse transcription polymerase chain reaction. A, normal control group; B, model control group; C1, C2 and C3, agmatine groups (20, 40 and 80 mg/kg, respectively). (B) Quantification of NMDAR1 mRNA expression of the five groups. The Y axis indicates the ratio of optical density (OD) of the samples to the corresponding internal standard (β-actin). Data are expressed as the mean ± standard error of the mean (n=10). *P<0.05, **P<0.01, compared with the normal control group. ΔP<0.01, for comparisons between the agmatine group and the model control group. NMDAR1, N-methyl-D-aspartic acid receptor; AGM, agmatine; PTZ, pentylenetetrazole.
Mentions: In order to analyze the alterations in the expression of the NMDA receptor induced by agmatine, RT-PCR was performed to detect NR1 and NR2b mRNA expression in the rat hippocampus (Fig. 4A). Compared with the model control group, the quantity of NR1 mRNA in the agmatine groups (40 and 80 mg/kg) was significantly decreased (P<0.01), suggesting that pretreatment with agmatine may suppress the actions of the hippocampal NR1 (Fig. 4B). However, the low-dose agmatine group (20 mg/kg) showed no significant difference compared with the model control group (Fig. 4B). In addition, no significant difference in NR2b mRNA expression was observed among all the groups (data not shown). These results indicated that treatment with higher concentrations of agmatine decreased the expression of the NMDA receptor.

Bottom Line: The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area.Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus.Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.

ABSTRACT
The aim of the present study was to investigate the mechanism underlying the effects of different doses of agmatine in rats with chronic epilepsy. To generate chronic epilepsy models, rats pretreated with different doses of agmatine (20, 40 and 80 mg/kg) were intraperitoneally injected with pentylenetetrazole (35 mg/kg) for 28 consecutive days. Epileptic behavior was observed using behavioral measurements of convulsion for 1 h after each treatment with pentylenetetrazole. Morphological alterations of the hippocampal neurons were also observed using hematoxylin and eosin staining. In addition, the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus were detected by immunohistochemistry. Furthermore, reverse transcription polymerase chain reaction was performed to detect the mRNA expression of two subunits (NR1 and NR2B) of the N-methyl-D-aspartic acid (NMDA) receptor in the rat hippocampus. The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area. Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus. Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Our results suggest that agmatine has an anticonvulsive effect in chronic epilepsy.

No MeSH data available.


Related in: MedlinePlus