Upregulation of klotho and erythropoietin contributes to the neuroprotection induced by curcumin-loaded nanoparticles in experimental model of chronic epilepsy.

Abstract

Klotho, which is a life extension factor, and erythropoietin (EPO) have been introduced as effective neuroprotective factors in several neurological disorders. The present study is an attempt to examine the potential role of klotho and EPO in therapeutic effect of curcumin-loaded nanoparticles (NPs) in pentylenetetrazol (PTZ)-induced kindling model. In order to induce the kindling model, PTZ was administrated intraperitoneally (i.p.) at dose of 36.5 mg/kg every other day for 20 days. Male NMRI mice received pre-treatment of free curcumin or curcumin-loaded NPs (12.5 mg/kg, i.p.) 10 days before PTZ injection and this was continued until 1 h before each PTZ injection. Immunostaining against NeuN, as a marker of neuronal maturation, and EPO was performed on hippocampal brain sections. Quantitative real time polymerase chain reaction (qRT-PCR) was conducted to assess the expression levels of tumor necrosis factor-α (TNF-α), klotho and EPO in the hippocampus. Immunostaining data indicated that treatment with curcumin-loaded NPs significantly alleviates the neuronal cell death in PTZ receiving animals. Curcumin-loaded NPs effectively upregulated the levels of EPO and klotho in PTZ receiving animals. Furthermore, mRNA level of TNF-α was considerably reduced in animals undergone curcumin-loaded NPs treatment. Overall, the results of this study suggest that downregulation of TNF-α and consequent upregulation of klotho and EPO might contribute to the neuroprotective effect of curcumin-loaded NPs in experimental model of epilepsy.

• Authors: Sahar Rostami Mansoor, Mona Hashemian, Mohsen Khalili-Fomeshi, Manouchehr Ashrafpour, Ali Akbar Moghadamnia, Maryam Ghasemi-Kasman
• Journal: Brain research bulletin (Brain Res Bull) Vol. 142 Pg. 281-288 (09 2018) ISSN: 1873-2747 [Electronic] United States
• PMID: 30130550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• Drug Carriers
• Epo protein, mouse
• Nerve Tissue Proteins
• NeuN protein, mouse
• Neuroprotective Agents
• Nuclear Proteins
• Tumor Necrosis Factor-alpha
• Erythropoietin
• Glucuronidase
• Klotho Proteins
• Curcumin
• Pentylenetetrazole

Topics

• Animals
• Chronic Disease
• Curcumin (administration & dosage)
• DNA-Binding Proteins
• Disease Models, Animal
• Drug Carriers
• Epilepsy (drug therapy, metabolism, pathology)
• Erythropoietin (metabolism)
• Glucuronidase (metabolism)
• Hippocampus (drug effects, metabolism, pathology)
• Kindling, Neurologic (drug effects)
• Klotho Proteins
• Male
• Mice
• Nanoparticles
• Nerve Tissue Proteins (metabolism)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotection (drug effects, physiology)
• Neuroprotective Agents (administration & dosage)
• Nuclear Proteins (metabolism)
• Pentylenetetrazole
• Random Allocation
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation (drug effects)