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Prenatal phencyclidine exposure alters hippocampal cell proliferation in offspring rats
Atsushi Tanimura1, Juan Liu, Takashi Namba
1Department of Psychiatry, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
Insights
Prenatal exposure to phencyclidine hydrochloride (PCP) in rats increased hippocampal cell proliferation in offspring. This neurogenesis alteration may contribute to behavioral abnormalities in infants exposed to PCP during pregnancy.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Phencyclidine hydrochloride (PCP) abuse during pregnancy is linked to infant abnormalities.
- The impact of prenatal PCP exposure on offspring neurodevelopment, particularly hippocampal neurogenesis, requires further investigation.
Purpose of the Study:
- To determine if chronic prenatal PCP exposure alters hippocampal neurogenesis in rat offspring.
- To assess the long-term effects of prenatal PCP exposure on cell proliferation and survival in the hippocampus.
Main Methods:
- Rats received daily subcutaneous injections of PCP (5 mg/kg) or saline during the final 2 weeks of gestation.
- Offspring neurogenesis was evaluated at 21 and 56 days postpartum using 5-bromo-2'-deoxyuridine (BrdU) labeling.
- Locomotor activity was assessed in offspring at 21 days postpartum.
Main Results:
- PCP-exposed offspring exhibited significantly increased BrdU-positive cells in the dentate gyrus granule cell layer at 21 days (77% increase) and 56 days (74% increase).
- Locomotor activity was significantly decreased by approximately 30% in PCP-exposed offspring at 21 days.
- Neuronal differentiation and cell survival were not affected at 5 weeks post-BrdU injection.
Conclusions:
- Chronic prenatal PCP exposure in rats leads to increased hippocampal cell proliferation in offspring.
- Altered hippocampal neurogenesis may underlie behavioral changes observed in infants prenatally exposed to PCP.
- Further research is needed to elucidate the biochemical and physiological mechanisms linking prenatal PCP exposure to altered neurogenesis and behavior.
Abstract:
Multiple case reports have described pregnancy in phencyclidine hydrochloride (PCP) abusers. Characteristic clinical symptoms of PCP-exposed infants have revealed neurobehavioral or physical abnormalities. We designed this study to evaluate whether chronic prenatal exposure to PCP during the last 2 weeks of gestation in rats produces alterations of hippocampal neurogenesis in offspring. Rats received repeated subcutaneous injection of PCP (5 mg/kg) once daily during the last 2 weeks of gestation. Control animals received subcutaneous injection of physiological saline during gestation. Dams receiving repeated PCP administrations showed markedly increased locomotor activities on days 1, 5, and 10 during the last 2 weeks of gestation. At 21 days after birth, 5-bromo-2'-deoxyuridine (BrdU)-positive cells of offspring were counted in the granule cell layer (GCL) and subgranular zone of the dentate gyrus. The numbers of BrdU-positive cells in the GCL in male and female offspring of the PCP-treated group were significantly increased by approximately 77% compared with those from the control group. At 56 days, the number of surviving BrdU-positive cells also remained to be increased by 74% in the GCL in PCP-treated group. At 21 days, locomotor activities of offspring in the PCP-treated group were significantly decreased by approximately 30% compared with those in the control group. However, neuronal differentiation of newly formed cells and cell survival were not influenced at 5 weeks after BrdU injections. Some altered biochemical or physiological conditions of offspring from dams receiving repeated PCP injections during pregnancy could influence changes in cell proliferation in the GCL of offspring during early development. Changes to cell proliferation in the hippocampus may affect behavioral abnormalities during infancy in offspring.
