Biology subjects

Dale, E.

Publications and source records attributed to Dale, E..

3 recordsLinked to original sources

bioRxiv2025

Microglial SWELL1 Deficiency Drives Male-Specific Seizure Vulnerability but Paradoxical Neuroprotection through Impaired Phagocytosis

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional knockout (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced lysosomal biogenesis contributed to the observed neuroprotection. These findings reveal novel roles for microglial VRAC in regulating seizure outcomes and microglia-neuron interactions.

neuroscience↗

bioRxiv2025

Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence

The remarkable cell diversity of multicellular organisms relies on the ability of multipotent progenitor cells to generate distinct cell types at the right times and locations during embryogenesis. A key question is how progenitors establish competence to respond to the different environmental signals required to produce specific cell types at critical developmental timepoints. We addressed this in the mouse developing forebrain, where neural progenitor cells must switch from producing neurons to making oligodendrocytes in response to increased Sonic Hedgehog (SHH) signaling during late embryogenesis. We show that progenitor responses to SHH are regulated by Notch signaling, thus permitting proper timing of the neuron-oligodendrocyte switch. Notch activity epigenetically primes genes associated with the oligodendrocyte lineage and SHH pathway, enabling amplified transcriptional responses to endogenous SHH and robust oligodendrogenesis. These results reveal a critical role for Notch in facilitating progenitor competence states and influencing cell fate transitions at the epigenetic level.

developmental biology↗

bioRxiv2024

Hearing thresholds in the bat Carollia perspicillata vary by sex but not age

Bats rely heavily on auditory perception for critical behaviors including navigation (echolocation) and conspecific communication. However, there is little information on the impacts of age and sex on the bat auditory system. Here, we used auditory brainstem response recordings to measure auditory thresholds in Carollia perspicillata (Sebas short-tailed bat). We did not detect an age-related threshold shift at the age range examined (1-8 years old), suggesting that bats may be relatively resistant to age-related hearing loss. We had considerably more young bats (aged 1-2 years) than older animals (aged 4-8 years) so our results should be interpreted with caution. However, they are consistent with other studies showing that bats exhibit fewer signs of aging relative to other small mammals. In addition, we show significantly lower auditory thresholds among females compared to age-matched males, similar to sex differences reported in other mammals. Finally, we found increased thresholds in a single non-pigmented bat relative to age- and sex-matched conspecifics. While preliminary, this finding suggests that pigmentation may be important for inner ear function in bats, similar to results from other mammals.

neuroscience↗