To better identify and understand the gene regulatory pathways associated with neurological diseases, researchers used Cre-Specific Nuclear Anchored Independent Labeling (cSNAIL), an improved, virus-based approach to isolating cell nuclei, to conduct assessments in mice. The researchers found “GPe PV + neuron-specific gene expression changes that indicate increased hypoxia-inducible factor 2 alpha (Hif2a) signaling”. The results were published in the Journal of Neuroscience.
Using cSNAIL, the researchers examined the cell-type-specific transcriptomic and epigenetic effects of dopamine depletion on PV + and PV- cells in three brain regions of male and female mice: GPe, striatum and cortex. The researchers also used the INTACT system with modifications.
The heterozygous and transgenic mice were injected with adeno-associated virus (AAV) and subjected to dopamine depletion surgery.
After staining, imaging and dissection, nuclei were extracted from the tissue and genetic analysis began.
The researchers identified “a transcriptional regulatory network mediated by the neuroprotective factor Hif2a as underlying differences in the nerve circuit in response to dopamine deficiency”.
GPe PV + neurons were the only cell population with notable changes in gene expression after dopamine deficiency from 6 cell populations.
“The evidence strongly supports an increase in HIF transcription factor activity in GPe PV + neurons after dopamine deficiency,” the authors say. “In the future, cSNAIL could be combined with protein assays to determine the accuracy [hypoxia-inducible factor] (HIF) protein expression levels, cellular localizations and DNA binding events in GPe PV + neurons in the presence of dopamine deficiency. ”
Lawler AJ, Brown AR, Bouchard RS et al. Cell-type-specific genomic signatures for oxidative stress in the globus pallidus of mice with dopamine deficiency. J Neurosci. 2020, November 10: JN-RM-1634-20. doi: 10.1523 / JNEUROSCI.1634-20.2020
This article originally appeared on Psychiatry Advisor
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