May 8, 2020

UCalgary researchers shine light on brain’s 'star' cells

Study reveals role of astrocytes in stress

An innovative study from scientists at the Cumming School of Medicine’s (CSM) Hotchkiss Brain Institute (HBI) at the University of Calgary place astrocytes — star-shaped brain cells known as “helper” cells — as drivers of the effects of stress in the brain. The study, led by Drs. Grant Gordon, PhD, and Jaideep Bains, PhD, with collaborators from the University of California Los Angeles and the Albert Einstein College of Medicine, was recently published in Nature Communications.

Drs. Jaideep Bains, Ciaran Murphy-Royal and Grant Gordon.

Drs. Jaideep Bains, Ciaran Murphy-Royal and Grant Gordon.

Jaideep Bains

Stress targets astrocytes

Astrocytes have multiple support roles within the brain. Key among these is the ability to supply the energy necessary for neurons, the brain cells within the nervous system, to communicate and store information.

Our study gives a fresh perspective, and provides new evidence that stress hormones disrupt information storage in the brain by targeting astrocytes,” says the study’s lead author Dr. Ciaran Murphy-Royal, PhD, an Alberta Innovates postdoctoral fellow and a Brain and Behaviour Research Foundation Fellow at the CSM. “Stress impairs a vital function of astrocytes, limiting their capacity to feed neighbouring neurons. This leads to a breakdown in neuronal function.”

Using a highly specialized imaging process called two-photon fluorescence, the scientists were able to watch astrocytes in various regions of the brain in mice and how those cells function when the stress hormone corticosterone is present. The team discovered that stress disrupts the shuttling of energy molecules through connected networks of astrocytes on their way to supply energy to neurons.

Images captured by a highly specialized imaging process called two-photon fluorescence show that stress reduces the movement of energy molecules through the astrocyte network.

Images captured by a highly specialized imaging process called two-photon fluorescence show that stress reduces the movement of energy molecules through the astrocyte network

Ciaran Murphy-Royal

Power failure in the brain

“We detected striking functional changes in the ability of astrocytes to move energy molecules, like lactate and glucose, from astrocyte to astrocyte, and ultimately found that astrocytes stopped feeding neurons after stress,” says Gordon, co-author of the study. “And when astrocytes didn’t feed neurons properly, information storage at synapses was disrupted.”

The disruption is similar to a breakdown at relay stations in an energy grid that results in unreliable power delivery to individual homes: manageable during times of low power demand, but problematic when power demand is high.

“In the brain, this means that neurons function properly most of the time, but during a time of high energy demand, for example when information has to be stored at connections between synapses, this fault in the relay stations means information storage is compromised,” says Gordon.

Further experiments reveal that by directly supplying lactate to a single astrocyte near these active synapses, the team could rescue this deficit in information storage.

The researchers say the study changes the way we think about how astrocytes may influence information storage in the brain under normal conditions, and may also shed light on astrocytes as a new therapeutic target for stress-linked brain disorders such as post-traumatic stress disorder or major depressive disorder.

VPR funding ignites research

The study was launched in 2017 with critical support from the Brain and Mental Health Strategic Research Fund established by the Office of the Vice-President (Research) to ignite innovative, multidisciplinary projects within the Brain and Mental Health research strategy.

“Our study required a myriad of expertise and perspectives. With the investment of the Brain and Mental Health Strategic Research Fund, we were able to build a team that included Dr. Murphy-Royal’s technical expertise along with scientists with two different fields of interest, astrocyte neurobiology and stress,” says Bains, a co-author of the study who is also a member of The Mathison Centre for Mental Health Research and Education at the CSM.

“Support for high-risk, novel projects is integral to expand research capacity at the University of Calgary and unlock new discoveries and treatments for brain health in our community.”

Jaideep Bains is a member of the HBI and the Mathison Centre for Mental Health Research and Education, a professor in the Department of Physiology and Pharmacology at the CSM, and was recently appointed deputy director for the university-wide Brain and Mental Health research strategy.

Grant Gordon is a member of the HBI and an associate professor in the Department of Physiology and Pharmacology at the CSM.

Led by the Hotchkiss Brain InstituteBrain and Mental Health is one of six research strategies guiding the University of Calgary toward its Eyes High goals. The strategy provides a unifying direction for brain and mental health research at the university.