Disease-vulnerable brain regions may lack adequate energy from the blood supply

Summary: Researchers say areas of the brain associated with neurodegenerative diseases tend to have less dense vascular networks that supply the brain with energy via blood. The findings shed light on how the neurovascular system plays a role in the development of neurodegeneration.

Source: Penn State

According to Penn State researchers, areas of the brain vulnerable to neurodegenerative disorders like Alzheimer’s disease tend to have less dense vascular networks – which supply the brain with energy via blood – than other areas of the brain.

They developed new maps showing how cells and vascular structures differ in various regions of the mouse brain, which may help them understand how vascular supply may be linked to neurological diseases.

Brain health relies on efficient energy supply and waste removal via the blood supplied by the body’s vascular system, which includes the veins and arteries. Although only 2% of body weight, the brain consumes about 20% of body energy.

The dysfunctional vasculature has been implicated in many neurodegenerative disorders. Yet scientists have limited knowledge about how the vasculature, which includes tiny microvessels, is organized in different areas of the brain, and about the relationship between the vasculature and major brain cell types, such as neurons.

The research team, led in part by Yongsoo Kim, associate professor of neural and behavioral sciences at Penn State College of Medicine, found that areas of the brain that process motor and sensory information have a high degree of vascularity.

They also found that association areas of the brain, where different information is synthesized and processed, tend to have a lower degree of vascularity.

“Loss or blockage of brain vessels, which occurs as people age, can further reduce energy supply to regions that have a less robust vascular network to begin with,” Kim said.

“As a result, neurons in association areas may experience accelerated cell death, which has been linked to cognitive decline.”

According to the researchers, studies aimed at mitigating cognitive decline have historically focused on targeting neurons to prevent cell loss, while less attention has been paid to understanding how the brain environment, namely the energy supply, contributes to neurodegenerative processes.

They hypothesize that neuronal loss during aging may be the result of a dysfunctional energy infrastructure in the brain.

Kim said studying the vasculature of the brain is challenging due to the small size of the vessels and cells that make up the vasculature and their intricate connections.

“It’s like understanding each thread of a spider’s web and its connections in three dimensions,” Kim said.

To understand how the vascular network is organized and understand its relationship to different types of neural cells in the mammalian brain, the team used high-resolution three-dimensional mapping methods to examine the complete structure of the vascular system, the pericytes (cells that control blood supply and vascular permeability) and major neuronal cell types in the adult mouse brain.

“Our approach is to generate a complete map similar to a Google map to see detailed cellular structures in the context of the entire mouse brain.”

Using complex algorithms and serial two-photon tomography, a technique for imaging a cross-section of an organism at single-cell resolution, Kim and colleagues generated maps of the vasculature in an entire mouse brain. They also genetically labeled different types of brain cells to compare the density and spatial location of vasculature in various regions.

Penn State researchers used advanced imaging to study vascular networks in the brain of an adult mouse. Credit: Penn State College of Medicine

They published their findings in Cell reports June 21st.

Given their finding that areas vulnerable to neurodegenerative diseases tend to have less dense vascular networks, Kim and his colleagues are comparing changes in the cerebral vascular network between normally aged mice and those with Alzheimer’s risk factors.

They hope to gather evidence to support their hypothesis that changes in brain vasculature can lead to neural dysfunction linked to cognitive decline. In the long term, their research could provide clues and therapeutic targets to prevent age-related brain damage.

“Understanding how energy balance and its dysfunction can lead to brain disorders could help prevent age-related neurodegeneration,” Kim said.

“Our study provides an essential baseline for examining the relationship between vascular networks and neuronal cell types and how changes in these systems may contribute to different brain disorders.”

See also

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About this neurodegeneration research news

Author: Zach Sweger
Source: Penn State
Contact: Zach Sweger – Pennsylvania State
Image: Image is credited to Penn State College of Medicine

Original research: Free access.
“Quantitative relationship between cerebrovascular network and neuronal cell types in mice” by Yuan-ting Wu et al. Cell reports


Quantitative relationship between cerebrovascular network and neuronal cell types in mice

Strong points

  • Resource for examining cerebral vasculature, pericytes and related neural subtypes
  • Dense cerebrovascular network in motor sensory circuits
  • Cortical vascularization significantly correlated with parvalbumin and nNOS neurons
  • Neurovascular architecture to respond to regionally distinct brain energy regulation


The cerebral vasculature and its wall cells must respond to the brain’s regional energy demands, but how their spatial relationship with different neuronal cell types varies across the brain remains largely unknown.

Here, we apply brain-scale mapping methods to comprehensively define the quantitative relationships between the cerebral vasculature, capillary pericytes, and glutamatergic and GABAergic neurons, including positive neuronal nitric oxide synthase (nNOS+) neurons and their subtypes in adult mice.

Our results show high densities of vasculature with high fluid conductance and capillary pericytes in primary motor sensory cortices compared to association cortices which show significant positive and negative correlations with energy-intensive parvalbumin+ and vasomotor nNOS+ neurons, respectively.

The thalamo-striatal areas that are connected to the primary motor sensory cortices also show high densities of vasculature and pericytes, suggesting dense energetic support for the motor sensory processing areas.

Our cellular resolution resource provides opportunities to examine the spatial relationships between the cerebrovascular network and neuronal cell composition in vastly understudied subcortical areas.

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