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Exploring mechanism of pioglitazone-induced memory restorative effect in experimental dementia.
Fundam Clin Pharmacol. 2009 Oct; 23(5):557-66.FC

Abstract

The present study was undertaken to investigate possible mechanism of pioglitazone-induced beneficial effect in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administration of streptozotocin (STZ; 3 mg/kg administered intracerebroventricularly on 1st & 3rd day). Morris Water-Maze test was employed to assess learning and memory of the animals. Brain acetylcholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Blood glucose level was also measured. Streptozotocin (STZ) produced a significant decrease in water-maze performance of mice hence reflecting loss of learning and memory. Pioglitazone (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits, without any significant per se effect on blood glucose levels. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in STZ treated animals, which were significantly attenuated by pioglitazone. Further, the noted beneficial effect of pioglitazone on STZ-induced dementia was significantly abolished by pre-treatment of nitric oxide (NO) synthase inhibitor L-NAME (3 mg/kg i.p.) manifested in the terms of decrease in water-maze performance and increase in brain AChE activity as well as oxidative stress. It is concluded that anti-dementic effect of pioglitazone may involve central cholinergic, oxidative and NO pathways.

Authors+Show Affiliations

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab PIN-147002, India.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19656209

Citation

Kaur, Baljinder, et al. "Exploring Mechanism of Pioglitazone-induced Memory Restorative Effect in Experimental Dementia." Fundamental & Clinical Pharmacology, vol. 23, no. 5, 2009, pp. 557-66.
Kaur B, Singh N, Jaggi AS. Exploring mechanism of pioglitazone-induced memory restorative effect in experimental dementia. Fundam Clin Pharmacol. 2009;23(5):557-66.
Kaur, B., Singh, N., & Jaggi, A. S. (2009). Exploring mechanism of pioglitazone-induced memory restorative effect in experimental dementia. Fundamental & Clinical Pharmacology, 23(5), 557-66. https://doi.org/10.1111/j.1472-8206.2009.00708.x
Kaur B, Singh N, Jaggi AS. Exploring Mechanism of Pioglitazone-induced Memory Restorative Effect in Experimental Dementia. Fundam Clin Pharmacol. 2009;23(5):557-66. PubMed PMID: 19656209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring mechanism of pioglitazone-induced memory restorative effect in experimental dementia. AU - Kaur,Baljinder, AU - Singh,Nirmal, AU - Jaggi,Amteshwar Singh, Y1 - 2009/07/28/ PY - 2009/8/7/entrez PY - 2009/8/7/pubmed PY - 2010/3/3/medline SP - 557 EP - 66 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 23 IS - 5 N2 - The present study was undertaken to investigate possible mechanism of pioglitazone-induced beneficial effect in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administration of streptozotocin (STZ; 3 mg/kg administered intracerebroventricularly on 1st & 3rd day). Morris Water-Maze test was employed to assess learning and memory of the animals. Brain acetylcholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Blood glucose level was also measured. Streptozotocin (STZ) produced a significant decrease in water-maze performance of mice hence reflecting loss of learning and memory. Pioglitazone (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits, without any significant per se effect on blood glucose levels. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in STZ treated animals, which were significantly attenuated by pioglitazone. Further, the noted beneficial effect of pioglitazone on STZ-induced dementia was significantly abolished by pre-treatment of nitric oxide (NO) synthase inhibitor L-NAME (3 mg/kg i.p.) manifested in the terms of decrease in water-maze performance and increase in brain AChE activity as well as oxidative stress. It is concluded that anti-dementic effect of pioglitazone may involve central cholinergic, oxidative and NO pathways. SN - 1472-8206 UR - https://www.unboundmedicine.com/medline/citation/19656209/Exploring_mechanism_of_pioglitazone_induced_memory_restorative_effect_in_experimental_dementia_ L2 - https://doi.org/10.1111/j.1472-8206.2009.00708.x DB - PRIME DP - Unbound Medicine ER -