Juvenile influenza can impair myelin development and adult behavior through chemokine signaling in mice

Juvenile influenza, specifically the H1N1 strain, can disrupt myelin development and lead to long-term cognitive and neuropsychiatric issues in mice, according to a recent study. This finding suggests that children may be especially vulnerable to such neural-immune challenges during their developmental years. To explore this phenomenon, juvenile mice were exposed to respiratory influenza infection.

Upon infection, white matter-specific microglial reactivity and oligodendrocyte loss were observed, persisting until two months post-infection. During this period, the mice exhibited hyperlocomotion and impaired attention, but not anxiety-like behavior. Genetic disruption of oligodendrocyte development at the same timepoint replicated these behavioral phenotypes.

Microglial reactivity and oligodendrocyte numbers returned to normal by young adulthood. However, myelin development was impaired, with decreased myelinated axon density and thinner myelin sheaths.

While hyperlocomotion resolved by two months after infection, anxiety-related behaviors emerged, indicating that while locomotion was restored, cognitive deficits persisted. Six months post-infection, anxiety was alleviated, but cognitive deficits remained. Elevated levels of chemokines in the cerebrospinal fluid (CSF) and microglial chemokine expression prompted further investigation into the role of the multi-chemokine receptor CCR3.

Inhibition of CCR3 rescued the cellular and behavioral aberrations following juvenile H1N1 infection.

In summary, this study highlights the potential for major immune challenges during the juvenile period to disrupt myelin development, leading to lasting cognitive and neuropsychiatric sequelae. Chemokine signaling emerges as a crucial therapeutic target in addressing these issues.