Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice

Abstract

Rationale

Animal studies have shown that early postnatal propofol administration is involved in neurobehavioral alterations in adults. However, the underlying mechanism is not clear.

Methods

We used c-Fos immunohistochemistry to identify activated neurons in brain regions of neonatal mice under propofol exposure and performed behavioral tests to observe the long-term consequences.

Results

Exposure to propofol (30g or 60 mg/kg) on P7 produced significant c-Fos expression in the deep layers of the piriform cortex on P8. Double immunofluorescence of c-Fos with interneuron markers in the piriform cortex revealed that c-Fos was specifically induced in calbindin (CB)-positive interneurons. Repeated propofol exposure from P7 to P9 induced behavioral deficits in adult mice, such as olfactory function deficit in a buried food test, decreased sociability in a three-chambered choice task, and impaired recognitive ability of learning and memory in novel object recognition tests. However, locomotor activity in the open-field test was not generally affected. Propofol treatment also significantly decreased the number of CB-positive interneurons in the piriform cortex of mice on P21 and adulthood.

Conclusions

These results suggest that CB-positive interneurons in the piriform cortex are vulnerable to propofol exposure during the neonatal period, and these neurons are involved in the damage effects of propofol on behavior changes. These data provide a new target of propofol neurotoxicity and may elucidate the mechanism of neurobehavioral deficits in adulthood.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81371197).

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Correspondence to Tiande Yang or Xiaotang Fan.

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Yu, D., Xiao, R., Huang, J. et al. Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice. Psychopharmacology 236, 657–670 (2019). https://doi.org/10.1007/s00213-018-5092-4

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Keywords

  • Propofol
  • Piriform cortex
  • c-Fos
  • Interneurons
  • Neurobehavioral function
  • Development