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Published on: November 20, 2015
Perinatal Penicillin Exposure Affects Cortical Development and Sensory Processing
James Perna1, Ju Lu1, Brian Mullen1
1Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, United States.
Insights
Early-life antibiotic exposure, like penicillin, can harm brain development in mice. These effects on sensory processing and neural activity persist into adulthood, impacting long-term brain function.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Antibiotic use in pregnancy and neonates is common, raising concerns about potential neurodevelopmental risks.
- The specific impact of early-life antibiotic exposure on the central nervous system remains poorly understood.
Purpose of the Study:
- To investigate the effects of perinatal penicillin exposure (PPE) on brain structure and function in a mouse model.
- To assess long-term consequences of PPE on behavior, neural activity, and synaptic development.
Main Methods:
- Mice received therapeutically relevant penicillin exposure during the perinatal period.
- Behavioral tests evaluated anxiety, working memory, and sensory processing.
- Immunohistochemistry, mesoscale calcium imaging, and two-photon imaging assessed neuronal and glial changes, neural activity, and synaptic plasticity.
Main Results:
- Adolescent mice exposed to PPE exhibited impaired sensory processing (texture discrimination, prepulse inhibition).
- PPE led to increased cortical neural activity, delayed maturation of inhibitory interneurons, and altered dendritic spine dynamics.
- Microglia showed increased density and altered morphology in PPE mice.
Conclusions:
- Perinatal penicillin exposure disrupts cortical development and alters neural circuit function.
- While synaptic defects may be transient, behavioral abnormalities persist into adulthood, indicating lasting neurodevelopmental effects.
Abstract:
The prevalent use of antibiotics in pregnant women and neonates raises concerns about long-term risks for children's health, but their effects on the central nervous system is not well understood. We studied the effects of perinatal penicillin exposure (PPE) on brain structure and function in mice with a therapeutically relevant regimen. We used a battery of behavioral tests to evaluate anxiety, working memory, and sensory processing, and immunohistochemistry to quantify changes in parvalbumin-expressing inhibitory interneurons (PV+ INs), perineuronal nets (PNNs), as well as microglia density and morphology. In addition, we performed mesoscale calcium imaging to study neural activity and functional connectivity across cortical regions, and two-photon imaging to monitor dendritic spine and microglial dynamics. We found that adolescent PPE mice have abnormal sensory processing, including impaired texture discrimination and altered prepulse inhibition. Such behavioral changes are associated with increased spontaneous neural activities in various cortical regions, and delayed maturation of PV+ INs in the somatosensory cortex. Furthermore, adolescent PPE mice have elevated elimination of dendritic spines on the apical dendrites of layer 5 pyramidal neurons, as well as increased ramifications and spatial coverage of cortical microglia. Finally, while synaptic defects are transient during adolescence, behavioral abnormalities persist into adulthood. Our study demonstrates that early-life exposure to antibiotics affects cortical development, leaving a lasting effect on brain functions.
