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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats

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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.

Frontiers in Molecular Neuroscience

|January 10, 2022

Summary

This summary is machine-generated.

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.

Keywords:

dendritic spine inhibitory interneuron microglia penicillin perineuronal net somatosensory cortex

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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.