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Updated: Jun 11, 2026
Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Behavioral consequences of NMDA antagonist-induced neuroapoptosis in the infant mouse brain
Carla M Yuede1, David F Wozniak, Catherine E Creeley
1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America. yuedec@psychiatry.wustl.edu
Insights
Exposure to phencyclidine (PCP), an NMDA antagonist, during early brain development causes lasting cognitive deficits. The timing and frequency of exposure significantly impact the severity of neuroapoptosis and long-term neurobehavioral outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- NMDA glutamate antagonists can induce neuroapoptosis during critical brain development periods.
- The developing human brain may be exposed to these antagonists via maternal drug use or anesthesia.
Purpose of the Study:
- To investigate the long-term neurobehavioral effects of early-life exposure to phencyclidine (PCP), an NMDA antagonist.
- To determine how the timing and frequency of PCP exposure influence neurodevelopmental outcomes.
Main Methods:
- Mice were exposed to a single dose of PCP or saline on postnatal day 2 (P2), P7, or both.
- Neurobehavioral effects and histological evidence of neuroapoptosis were evaluated.
Main Results:
- PCP exposure on both P2 and P7 resulted in more severe cognitive impairments than single-day exposure.
- The pattern of neuroapoptosis differed between P2 and P7 exposures.
- Pups exposed on P2 showed greater damage on P7 compared to those exposed only on P7.
Conclusions:
- PCP induces distinct patterns of neuroapoptosis based on the developmental age at exposure.
- Exposure to PCP at two separate developmental ages leads to more severe neuropathological and neurobehavioral consequences than single exposure.
Background:
Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia.
Methodology/Principal Findings:
We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7.
Conclusions:
These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathological and neurobehavioral consequences than a single treatment.
