Summary: A new study identifies the brain protein vesicular nucleotide transporter (Vnut) as essential for regulating mood and motivation in mice. When Vnut was removed from brain cells called astrocytes, the mice, especially females, showed higher anxiety, depression-like behavior, and decreased motivation.
This effect was associated with a decrease in dopamine, a key molecule for motivation and positive mood. These findings suggest that Vnut plays an important role in dopamine regulation, with potential implications for understanding mood disorders.
Important facts:
Removing Vnut from astrocytes increased anxiety and depression-like behavior in mice. Female mice lacking Vnut had significantly reduced reward motivation, a trait associated with depression. This effect was associated with a decrease in dopamine levels, which is key to motivation and emotional regulation.
Source: University of Kentucky
Researchers at the University of Kentucky were part of a team that discovered a key protein in the brain that can modulate reward motivation in mice.
The study, titled “Deletion of mouse astrocyte vesicle nucleotide transporters increases anxiety and depression-like behavior and weakens reward motivation,” was published in the journal Molecular Psychiatry.
“This research investigates important regulators of brain activity through a variety of mechanisms. Ultimately, a deeper understanding of this may lead to new treatments for neurological and psychiatric diseases. ,” said Wei-Kang Cai, Ph.D., associate professor in the School of Medicine’s Department of Molecular and Cellular Biochemistry and professor in the Barnstable Department of Brown Diabetes Medicine. Obesity Research Center (BBDOC).
Kai is also the principal investigator on a grant from the National Institute of Mental Health that supported this research. He collaborated with Dr. Qian Huang, a research assistant professor in the Department of Molecular and Cellular Biochemistry and lead author of the paper.
A team of scientists investigated astrocytes, a type of brain cell that supports the central nervous system. These cells are known to release molecules to communicate with neurons and are necessary for proper brain function.
For example, a protein called vesicular nucleotide transporter (Vnut) mediates the release of ATP, a specific molecule that normally provides energy to cells. The researchers wanted to know whether ATP released through Vnuts was important for brain function.
To investigate the functional significance of Vnut, the researchers removed the protein from astrocytes in a mouse model and analyzed the mice’s behavior. The researchers found that deletion of this protein did not alter brain structure, metabolism, or memory.
The research team also investigated the loss of Vnut in anxiety and depression-like behaviors in mice through open field and reward tests.
“We found that loss of Vnut in adult mice led to increased anxiety, depression-like behavior, and, more importantly, decreased reward motivation, especially in females,” Cai said.
The researchers said that in open field trials, female mice spent most of their time facing the wall rather than in the open area, indicating an anxious attitude.
“This study shows that loss of Vnut in astrocytes is sufficient to induce depression-like behavior in mice,” Huang said. “The same mechanisms at work here may be involved in depression in humans.”
The scientists noted changes in behavioral variables in the mice, particularly a lack of interest and increased immobility during a swimming test.
Finally, to assess reward motivation, the researchers trained mice to poke their noses into a device to obtain food pellets containing sucrose. Sweetened food pellets provide a strong reward to normal mice.
When the difficulty of the task increased or when more pokes were needed to obtain food, normal females continued to work to obtain the reward pellet. In stark contrast, women lacking Vnut were able to give up on the task faster. This means they are less motivated by rewards. This is often a clinical sign of major depression in humans.
Importantly, Tsai’s research group found that the cause of reduced reward motivation is reduced levels of dopamine, a “happy” molecule in the brain that is important for motivated behavior in both rodents and humans. This is what we discovered.
The results of this study show that Vnut is a protein important in regulating dopamine signals, mood, and motivation in the brain, and its loss leads to functional effects such as anxiety, depressive-like behavior, and decreased reward motivation. Suggests.
“This discovery helps us understand how specific proteins in specific brain regions influence emotion and behavior and provides a new approach for future research on mood disorders,” Cai said. Ta.
About this neuroscience research news
Author: Sara Macias Palacio
Source: University of Kentucky
Contact: Sara Macias Palacio – University of Kentucky
Image: Image credited to Neuroscience News
Original research: Closed access.
“Deletion of the astrocyte vesicle nucleotide transporter in mice increases anxiety and depression-like behavior and weakens reward motivation” by Qian Huang et al. Molecular Psychiatry
abstract
Deletion of astrocyte vesicle nucleotide transporters in mice increases anxiety and depression-like behavior and weakens reward motivation
Astrocytes are multifunctional glial cells of the central nervous system that play important roles in regulating metabolism, extracellular ion and neurotransmitter levels, and synaptic plasticity.
Astrocyte-derived signaling molecules mediate many of these regulatory functions of astrocytes, including vesicular release of ATP. In this study, we used a unique genetic mouse model to investigate the functional significance of astrocyte exocytosis of ATP.
Using primary cultured astrocytes, we demonstrated that when the vesicular nucleotide transporter (Vnut), a primary transporter responsible for loading cytoplasmic ATP into secretory vesicles, is lost, the molecular mechanism of exocytosis remains unchanged. , showed that ATP loading into secretory lysosomes and ATP release were dramatically reduced. or total intracellular ATP content.
Deletion of Vnut in astrocytes in adult mice, especially in females, results in increased anxiety, depressive-like behavior, and reward sensitivity without significantly affecting food intake, whole-body glucose metabolism, cognition, or sociability. This causes a decrease in motivation.
These behavioral changes are associated with a significant decrease in basal extracellular dopamine levels in the nucleus accumbens. Similarly, ex vivo brain slices from these mice show a strong trend toward decreased evoked dopamine release in the nucleus accumbens.
Mechanistically, the decrease in dopamine signaling that we observed may be due to increased expression of monoamine oxidase.
Taken together, these data demonstrate an important regulatory role for astrocytic exocytosis of ATP in anxiety, depressive-like behavior, and reward motivation by modulating mesolimbic dopamine circuits.
