Biology subjects

Zernicka-Glover, N. K.

Publications and source records attributed to Zernicka-Glover, N. K..

2 recordsLinked to original sources

bioRxiv2026

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

Brain development, especially developmental myelination, continues through young adulthood. Concordantly, children may be particularly vulnerable to neural-immune challenges. To investigate the consequences of major childhood immune challenges, juvenile mice were exposed to respiratory influenza (H1N1) infection. White matter-specific microglial reactivity accompanied by oligodendrocyte loss was evident until two months following infection. Mice exhibited hyperlocomotion and impaired attention, but not anxiety-like behavior, at one month following infection. Linking the oligodendroglial and behavioral deficits, genetic disruption of oligodendrocyte development at the same juvenile timepoint recapitulated this behavioral phenotype. Microglial reactivity and oligodendrocyte numbers normalized by young adulthood. However, myelin development was disrupted, with persistently decreased myelinated axon density and reduced myelin sheath thickness. Hyperlocomotion resolved, but anxiety-related behaviors emerged at two months after infection. At 6 months, anxiety resolved but cognitive deficits persisted. Elevated CSF chemokines and microglial chemokine expression prompted testing the role of the multi-chemokine receptor CCR3. CCR3 inhibition rescued these cellular and behavioral aberrations after juvenile H1N1 infection. Together, these findings underscore the potential for disruption of myelin development and lasting cognitive and neuropsychiatric sequelae following major immune challenges during the juvenile period and highlight chemokine signaling as an important therapeutic target.

neuroscience↗

bioRxiv2024

Calcium dynamics tune developmental tempo to generate evolutionarily divergent axon tract lengths

The human brain has undergone an evolutionary expansion in size, both in terms of cell numbers and the size of cellular structures, including axon tracts. Human brain development also progresses slowly and takes particularly long. However, the functional relevance of slowed timing, and whether it is responsible for these changes in size, remains unknown. Here, we investigate this by studying axon tract development in human and mouse brain organoids. We demonstrate that human axon tracts grow [~]2x more slowly than those of mice, reflecting their slowed tempo, but that this actually leads to shorter human axons, not longer. To overcome the effect of slowed tempo, human axons have a more prolonged growth duration that enables them to project farther despite their slower growth rate. Using a combination of single-cell RNA sequencing and live imaging, we demonstrate that the prolonged duration involves a different mechanism to that controlling tempo and is driven by calcium dynamics. Human axons exhibit a reduced calcium influx compared to mouse, mediated by L-Type voltage-gated calcium channels. Stimulating this calcium influx in human neurons triggers earlier cessation of growth, leading to shorter axon tracts similar to those of mouse. We further show that increasing calcium speeds up the transition to the synaptogenesis stage. Thus, calcium regulation sets the timing of transitions to disproportionately extend developmental duration, thereby enabling evolutionary expansion of human neurons.

developmental biology↗