Dose-dependent effects of prenatal exposure of pioglitazone, the PPARγ agonist, on the hippocampus development and learning and memory performance of rat offspring

It is known that pioglitazone, defined as a PPAR gamma agonist, has neuron-protective properties in nervous system disorders. The aim of this study is to investigate the effects of pioglitazone administration at different doses during prenatal period on the neurons, glial cells and learning-memory levels in the hippocampus of rat offspring. Pregnant rats were divided into three groups; Low-Dose Pioglitazone (LDP), High-Dose Pioglitazone (HDP) and control (C) (n = 3). Pregnant rats in the HDP and LDP groups were given pioglitazone at 30 mg/kg and 5 mg/ kg doses, respectively, by gavage once a day during their pregnancy. No procedure was applied to the rats in the control group. Morris water tank test was applied to offspring obtained from postnatal 24th to 28th day. The offspring were sacrificed on the 29th postal day and their brain tissues removed. Stereological, histopathological and immunohistochemical techniques were used to analyze brain tissues. As a result of the analysis, it was observed that there were delays in learning and memory, the number of pyramidal neurons decreased, and the density of cells stained with glial fibrillar acidic protein (GFAP) positive increased in the HDP group compared to the other groups (p < 0.05). No significant difference was found between the LDP and control groups in terms of these parameters (p > 0.05). Our results showed that pioglitazone administered in the prenatal period had an effect on the hippocampus development and learning and memory performance of rats, depending on the dose.

Automated summary

The study found that using pioglitazone at different doses during pregnancy can affect the neurons, glial cells, and learning-memory levels in the hippocampus. The high-dose group showed delays in learning and memory, decreased number of pyramidal neurons, and increased density of GFAP-positive cells, while the low-dose group did not show significant differences compared to the control group.