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Effect of Androsterone after Pilocarpine-induced Status Epilepticus in Mice.

Cho I, Cho YJ, Kim HW, Heo K, Lee BI, Kim WJ - J Epilepsy Res (2014)

Bottom Line: Neurosteroids exert their antiepileptic effects via GABAA and NMDA receptors.The number of CB-positive cells was 1±0.4 cells/mm(3) in pilocarpine-only group, 14±1.1 cells/mm(3) in pilocarpine plus androsterone 100 mg group and 29±2.5 cells/mm(3) in pilocarpine plus androsterone 200 mg group (p<0.001).These results suggest that the neuroprotective effect of androsterone after pilocarpine- induced SE may be mediated by an increased expression of CB.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea ; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.

ABSTRACT

Background and purpose: Neurosteroids exert their antiepileptic effects via GABAA and NMDA receptors. Another cell death mechanism is excessive Ca(2+) influx into cells. Calbindin-D28k (CB) is a protein that modulates intracellular Ca(2+) in the nervous system. We evaluated whether androsterone up-regulates the expression of CB and has a neuroprotective effect by controlling Ca(2+) after pilocarpine-induced status epilepticus (SE) in mice.

Methods: SE was induced in ICR mice by injection of pilocarpine. Two hours after SE, mice were treated intraperitoneally (i.p.) with androsterone (100-200 mg/kg) or vehicle, and compared with other control groups. Two days after injection, immunohistochemical staining for CB was performed using a hippocampal slice from each mice group. We also used cresyl violet staining to compare changes in hippocampal structures.

Results: Two days after pilocarpine-induced SE, androsterone increased the expression of CB in the hippocampus compared with control SE mice. The number of CB-positive cells was 1±0.4 cells/mm(3) in pilocarpine-only group, 14±1.1 cells/mm(3) in pilocarpine plus androsterone 100 mg group and 29±2.5 cells/mm(3) in pilocarpine plus androsterone 200 mg group (p<0.001).

Conclusions: These results suggest that the neuroprotective effect of androsterone after pilocarpine- induced SE may be mediated by an increased expression of CB.

No MeSH data available.


Related in: MedlinePlus

(A) Representative CB-immunostained hippocampi from the normal group (a, e, i), pilocarpine-only group (b, f, j), pilocarpine plus androsterone 200 mg group (c, g, k), and androsterone-only group (d, h, l). In the pilocarpine plus androsterone group, CB-positive neurons increased in the stratum radiatum of the CA1 and CA3 regions, the stratum lucidum of the CA3 region, and the stratum molecular of the DG compared to the other groups. Insets show the high-magnified images c, e, g and k. (B) Quantitation of CB-positive cells in the stratum radiatum of hippocampus. In the pilocarpine plus androsterone groups, CB-positive interneuron cells increased dose dependently. *p<0.001
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f4-er-4-1-7-2: (A) Representative CB-immunostained hippocampi from the normal group (a, e, i), pilocarpine-only group (b, f, j), pilocarpine plus androsterone 200 mg group (c, g, k), and androsterone-only group (d, h, l). In the pilocarpine plus androsterone group, CB-positive neurons increased in the stratum radiatum of the CA1 and CA3 regions, the stratum lucidum of the CA3 region, and the stratum molecular of the DG compared to the other groups. Insets show the high-magnified images c, e, g and k. (B) Quantitation of CB-positive cells in the stratum radiatum of hippocampus. In the pilocarpine plus androsterone groups, CB-positive interneuron cells increased dose dependently. *p<0.001

Mentions: We also compared CB changes after pilocarpine-induced SE. CB-positive cells were increased in all subfields of hippocampus in the pilocarpine plus androsterone group compared to the pilocarpine-only group (Fig. 3). In particular, CB-positive cells increased dose-dependently in the pilocarpine plus androsterone group, the stratum radiatum of the CA1 and CA3 region, the stratum lucidum of the CA3 region (Fig. 3D to I), and the stratum molecular of the DG (Fig. 3J to L). In the pilocarpine-only group, CB-positive cells were dramatically reduced in the entire hippocampus. Especially in the stratum radiatum of the CA1 and CA3 regions, expression of CB-positive cells, such as interneurons, was reduced in pilocarpine-only group compared to the normal control group. Additionally, the CB staining intensity was decreased in the stratum lucidum of the CA3 region (Fig. 4).


Effect of Androsterone after Pilocarpine-induced Status Epilepticus in Mice.

Cho I, Cho YJ, Kim HW, Heo K, Lee BI, Kim WJ - J Epilepsy Res (2014)

(A) Representative CB-immunostained hippocampi from the normal group (a, e, i), pilocarpine-only group (b, f, j), pilocarpine plus androsterone 200 mg group (c, g, k), and androsterone-only group (d, h, l). In the pilocarpine plus androsterone group, CB-positive neurons increased in the stratum radiatum of the CA1 and CA3 regions, the stratum lucidum of the CA3 region, and the stratum molecular of the DG compared to the other groups. Insets show the high-magnified images c, e, g and k. (B) Quantitation of CB-positive cells in the stratum radiatum of hippocampus. In the pilocarpine plus androsterone groups, CB-positive interneuron cells increased dose dependently. *p<0.001
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Related In: Results  -  Collection

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f4-er-4-1-7-2: (A) Representative CB-immunostained hippocampi from the normal group (a, e, i), pilocarpine-only group (b, f, j), pilocarpine plus androsterone 200 mg group (c, g, k), and androsterone-only group (d, h, l). In the pilocarpine plus androsterone group, CB-positive neurons increased in the stratum radiatum of the CA1 and CA3 regions, the stratum lucidum of the CA3 region, and the stratum molecular of the DG compared to the other groups. Insets show the high-magnified images c, e, g and k. (B) Quantitation of CB-positive cells in the stratum radiatum of hippocampus. In the pilocarpine plus androsterone groups, CB-positive interneuron cells increased dose dependently. *p<0.001
Mentions: We also compared CB changes after pilocarpine-induced SE. CB-positive cells were increased in all subfields of hippocampus in the pilocarpine plus androsterone group compared to the pilocarpine-only group (Fig. 3). In particular, CB-positive cells increased dose-dependently in the pilocarpine plus androsterone group, the stratum radiatum of the CA1 and CA3 region, the stratum lucidum of the CA3 region (Fig. 3D to I), and the stratum molecular of the DG (Fig. 3J to L). In the pilocarpine-only group, CB-positive cells were dramatically reduced in the entire hippocampus. Especially in the stratum radiatum of the CA1 and CA3 regions, expression of CB-positive cells, such as interneurons, was reduced in pilocarpine-only group compared to the normal control group. Additionally, the CB staining intensity was decreased in the stratum lucidum of the CA3 region (Fig. 4).

Bottom Line: Neurosteroids exert their antiepileptic effects via GABAA and NMDA receptors.The number of CB-positive cells was 1±0.4 cells/mm(3) in pilocarpine-only group, 14±1.1 cells/mm(3) in pilocarpine plus androsterone 100 mg group and 29±2.5 cells/mm(3) in pilocarpine plus androsterone 200 mg group (p<0.001).These results suggest that the neuroprotective effect of androsterone after pilocarpine- induced SE may be mediated by an increased expression of CB.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea ; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.

ABSTRACT

Background and purpose: Neurosteroids exert their antiepileptic effects via GABAA and NMDA receptors. Another cell death mechanism is excessive Ca(2+) influx into cells. Calbindin-D28k (CB) is a protein that modulates intracellular Ca(2+) in the nervous system. We evaluated whether androsterone up-regulates the expression of CB and has a neuroprotective effect by controlling Ca(2+) after pilocarpine-induced status epilepticus (SE) in mice.

Methods: SE was induced in ICR mice by injection of pilocarpine. Two hours after SE, mice were treated intraperitoneally (i.p.) with androsterone (100-200 mg/kg) or vehicle, and compared with other control groups. Two days after injection, immunohistochemical staining for CB was performed using a hippocampal slice from each mice group. We also used cresyl violet staining to compare changes in hippocampal structures.

Results: Two days after pilocarpine-induced SE, androsterone increased the expression of CB in the hippocampus compared with control SE mice. The number of CB-positive cells was 1±0.4 cells/mm(3) in pilocarpine-only group, 14±1.1 cells/mm(3) in pilocarpine plus androsterone 100 mg group and 29±2.5 cells/mm(3) in pilocarpine plus androsterone 200 mg group (p<0.001).

Conclusions: These results suggest that the neuroprotective effect of androsterone after pilocarpine- induced SE may be mediated by an increased expression of CB.

No MeSH data available.


Related in: MedlinePlus