Early resource scarcity drives persistent transcriptional changes and vascular remodeling in the female prefrontal cortex
Year: 2026
Type: preprint
Abstract: Early childhood poverty is an environmental risk factor for psychiatric and neurodegenerative disorders, yet the cellular mechanisms by which resource scarcity produces persistent brain vulnerability remain poorly understood. The medial prefrontal cortex (mPFC), which regulates executive function and motivated behavior, is sensitive to early environmental conditions. To identify mechanisms linking early resource scarcity to lasting mPFC dysfunction, we used the rat limited bedding and nesting (LBN) model, which recapitulates key features of poverty. Prior work shows LBN disrupts mPFC-mediated behaviors in adulthood, often in a sex-specific manner. Here, we used single-nucleus RNA sequencing (snRNAseq) to identify sex- and cell-type-specific transcriptional alterations in the adult mPFC following brief postnatal LBN exposure or control housing. LBN induced more differentially expressed genes (DEGs) across multiple pyramidal neuron clusters in females than in males. Unexpectedly, the largest transcriptional changes due to LBN occurred in vascular cells in females, whereas male vascular cells exhibited no DEGs. These female-specific vascular genes were enriched for alterations of transcriptional programs regulating angiogenesis and endothelial structure. This molecular profile was orthogonally validated with 3D vascular reconstruction, revealing LBN reduced vascular coverage in the adult female mPFC, driven by decreased vessel volume and shortened vessel length, while males were unaffected. Reduced vascular coverage may constrain metabolic support to this region. The postnatal period is a critical window for vascular maturation, and, taken together, these findings identify persistent, female-specific vascular alterations as a novel and previously unrecognized mechanism through which early resource scarcity may persistently affect brain function and vulnerability.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Zeiss LSM 980 with Airyscan 2 for Imaging Core Facility, Sex differences in corticotropin releasing factor regulation of the septohippocampal memory circuit, Determining the effect of early resource scarcity on adolescent addiction-related behavior and cell-type specific transcription, Sex differences in stress inoculation of addiction-like phenotypes, Delineating the epigenetic and neural mechanisms by which early life scarcity alters motivated behavior, Early life pain and its modulation by socioenvironmental factors: Implications for substance misuse, Lasting effects of early resource scarcity on cortical astrocyte structure and function
OpenAlex ID: W7164505934