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Influence of Chronically Activated Neuroendocrine Stress Pathways on Vascular Supply and Metabolic Demand in the Hippocampus
Fattore, Jake
Fattore, Jake
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Abstract
Chronic psychological stress is known to heavily influence the hippocampus (HPC), a region primarily involved in memory and learning, and is correlated with the onset of prevalent neurodegenerative diseases such as Alzheimer’s disease (AD) and vascular dementia (VaD), and age-related cognitive decline (Alzheimer's Disease Facts and Figures, 2024; Bisht et al., 2018; Gowda et al., 2022). Although progress has been made on understanding the effects of chronic stress on hippocampal vascular function, little is known about the possible effects of chronic stress on the balance of blood supply and energy demand in the HPC as it pertains to baseline vascular architecture and density. Here, we use a novel experimental rat model to chronically activate neuroendocrine stress pathways by genetically manipulating neuronal mechanisms in the paraventricular nucleus (PVN) of the hypothalamus to mimic the neuroendocrine and cardiovascular changes induced by chronic stress and observe the effects on hippocampal function. We examined and measured changes in vascular architecture, mitochondrial, and synaptic densities in the cornu ammonis 3 (CA3) , polymorph layer (PoDG), granule cell layer (GCL), and molecular layer (MoDG) of the dentate gyrus (DG) in the HPC to further understand how chronic stress may promote dementias by disrupting the balance of blood supply versus energy demand in the HPC. Our results show a significant increase in mitochondrial density within the MoDG of the HPC in rats whose primary neuroendocrine stress pathways were chronically activated through injection of a viral vector containing BDNF mRNA into the PVN and no significant differences in vascular or synaptic density between groups. These findings suggest prolonged activation of neuroendocrine stress pathways and associated hypertension via PVN-BDNF viral vector injection may impair hippocampal integrity by limiting the vascular network’s ability to adapt and meet elevated metabolic demand.
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2026-05-08
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Department of Pharmacology