Volume 75 (2025) Issue: 2025 No#2

The effects of perinatal phencyclidine administration on the density and branching of astrocytes in the brain of aged rats

Author(s): Sava Ivaz, Nela Puškaš, Bojana Paunović, Tihomir Stojković, Tatjana Nikolić, Milica Velimirović Bogosavljević, Milica Živković, Nataša Petronijević

Keywords:Ageing; Astrocytes; Glial fibrillary acidic protein – GFAP; Phencyclidine; Schizophrenia

Phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate glutamate receptor (NMDA-R), is used for modeling schizophrenia in animals, as NMDA-R hypofunction is vital in its pathophysiology. Recent studies have shown that glial fibrillary acidic protein (GFAP), an astrocyte marker, is altered in the prefrontal cortex and in certain hippocampal regions in individuals with schizophrenia. To our knowledge, no study has examined long-term effects (in aged rats) of perinatal PCP treatment on the density and branching of astrocytes. The aim of this study was to compare the density and branching of astrocytes in the dentate gyrus (DG), CA1 and CA2/3 regions of the hippocampus, and in the medial prefrontal cortex (mPFC) of 18-month-old rats treated perinatally with PCP compared to saline (NaCl) control group. Male Wistar rats (n=6) were treated with PCP (10 mg/kg) on postnatal days (PND) 2, 6, 9 and 12, while the control group (n=6) received NaCl on the same PNDs. All rats were sacrificed at 18 months of age (PND540). Astrocytes were visualized using GFAP immunohistochemistry. Results show that astrocyte density in PCP-treated rats was significantly lower compared to the NaCl group in DG (p<0.01) and CA2/3 regions (p<0.01) and mPFC (p<0.05). There were no changes in the branching of the astrocytes in any of the structures investigated. Our finding of a significant decrease in astrocyte density in the hippocampus and mPFC in aged rats perinatally treated with PCP, indicates that astrocytes may be involved in the morphological and functional impairments in these brain regions, caused by NMDA-R dysfunction.