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

Highlights: • Prenatal exposure to high-dose pioglitazone caused neuronal loss in the hippocampus and increased GFAP (+) cell density. • Hippocampal damage induced by high dose pioglitazone caused impairments in learning and memory in offspring. • Prenatal exposure to low-dose piogitazone did not cause hippocampal damage in offspring. It is known that pioglitazone, defined as a PPARγ 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.