Identifying and understanding critical periods in brain development is essential to decoding the long-term impact of widespread, poorly defined, and frequently occurring insults such as inflammation.
The cerebellum is increasingly appreciated for its role in social, emotional, and cognitive behaviors.
‘Consequences of inflammation locally in the cerebellum are prevented by peripheral treatment with the cyclooxygenase inhibitor or the aromatase inhibitor.’
In neuropsychiatric disorders such as autism spectrum disorder and schizophrenia that originate during brain development, the cerebellum is consistently and severely affected.
Using the laboratory rat, researchers have discovered a narrowly constrained critical period of brain development, that is Purkinje neuron development, which is subjected to dysregulation by inflammation, during the second week of life.
This critical period is determined by gene expression profile present only during the second postnatal week and not the first or third weeks.
When inflammation occurs during the second postnatal week, it results in stunted dendrites of the cerebellum's principal neurons, Purkinje cells, and impairments in later social behavior.
Genes expressed during this time code for enzymes and receptors which are critical not only for prostaglandin production and activity but also for estradiol production and estradiol action.
Dysregulation of the prostaglandin E2 (PGE2)-estradiol pathway during the second week by treatment with PGE2 or lipopolysaccharides produces enduring consequences as a result of reduced growth of Purkinje dendritic trees and impaired juvenile social play behavior, but only in males.
The deleterious consequences of inflammation locally in the cerebellum are prevented by peripheral treatment with the cyclooxygenase inhibitor nimesulide or the aromatase inhibitor formestane.
These findings published in the Journal of Neuroscience
highlight a novel regulatory pathway that creates a critical period in brain development vulnerable to dysregulation by inflammation.
These changes are not evident if inflammation occurs during the first or third week, highlighting the importance of fine-grained analyses of developmental processes and the factors that influence them.