PPARγ Agonist Pioglitazone Reverses Memory Impairment and Biochemical Changes in a Mouse Model of Type 2 Diabetes Mellitus
| Autor: | Jia-chang Li, Yan Long, Li-Ying Jiang, Hao Hong, Ming-Xing Liao, Qi-Long Ding, Mei Hu, Wei Hu, Li-Ping Liu, Su-Su Tang, Xiao-Yun Wang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pharmacology
Agonist medicine.medical_specialty endocrine system diseases medicine.drug_class business.industry nutritional and metabolic diseases Morris water navigation task Type 2 Diabetes Mellitus medicine.disease Streptozotocin Hypoinsulinemia Psychiatry and Mental health Endocrinology Physiology (medical) Diabetes mellitus Internal medicine medicine Pharmacology (medical) Receptor business Pioglitazone medicine.drug |
| Zdroj: | CNS Neuroscience & Therapeutics. 18:659-666 |
| ISSN: | 1755-5930 |
| DOI: | 10.1111/j.1755-5949.2012.00341.x |
| Popis: | SUMMARY Aims: Pioglitazone, known as a peroxisome proliferator-activated receptor γ (PPARγ) agonist, is used to treat type 2 diabetes mellitus (T2DM). T2DM has been associated with reduced performance on numerous domains of cognitive function. Here, we investigated the effects of pioglitazone on memory impairment in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. Methods: ICR mice were fed with HFD for 4 weeks and then injected with a single low dose of STZ followed by continued HFD feeding for an additional 4 weeks. Pioglitazone (18 mg/kg, 9 mg/kg body weight) was orally administered for 6 weeks once daily. Y-maze test and Morris water maze test (MWM) were employed for testing learning and memory. Serum glucose, serum insulin, serum triglyceride, brain β-amyloid peptide (Aβ), brain β-site amyloid precursor protein cleaving enzyme (BACE1), brain nuclear factor κB (NF-κB), and brain receptor for advanced glycation end products (RAGE) were also tested. Results: The STZ/HFD diabetic mice, characterized by hyperglycemia, hyperlipemia and hypoinsulinemia, performed poorly on Y-maze and MWM hence reflecting impairment of learning and memory behavior with increases of Aβ40/Aβ42, BACE1, NF-κB, and RAGE in brain. Treatment of PPARγ agonist, pioglitazone (18 or 9 mg/kg body weight), significantly reversed diabetes-induced impairment of learning and memory behavior, which is involved in decreases of Aβ40/Aβ42 via inhibition of NF-κB, BACE1 and RAGE in brain as well as attenuation of hyperglycemia, hyperlipemia, and hypoinsulinemia. Conclusions: It is concluded that PPARγ agonist pioglitazone may be considered as potential pharmacological agents for the management of cognitive dysfunction in T2DM. |
| Databáze: | OpenAIRE |
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