Mice and Mental Health: New Mouse Studies May Help Us Understand Depression, Schizophrenia and Other Mental Disorders
For more than 150 years, researchers have used laboratory mice to study various physical diseases and conditions that occur in humans, in part because changes in the body of a rodent are relatively easy to control and study.
Using mice to study mental conditions has been more challenging, however, because the mouse mind doesn’t experience some mental illnesses that are distinctly human, and because mice can’t report their own symptoms or tell us what they are experiencing.
Now, however, new research has revealed some important insights into human mental illnesses, including depression, schizophrenia, and psychosis.
Depression and the Gut-Brain Connection
According to recent research, depression isn’t all in your head. Not only is it a very real mental disorder, it might not stem from your brain at all, but rather your gut.
Over the last few years, scientists have been increasingly focused on the gut and the microbes that live there as an important factor in human health. Bacterial imbalances in the gut have already been linked to cancer, autism, Parkinson’s disease, and many other conditions.
Now, a new study from the University of Virginia has found another brain-got connection: a good bacteria commonly found in yogurt can help relieve depression-like symptoms in mice.
The researchers subjected several groups of mice to different stressors until the mice started exhibiting “despair behavior.” Then they collected and analyzes fecal samples from the stressed mice.
All samples showed a significant reduction in Lactobacillus, the same microbe found in yogurt. By adding Lactobacillus back into the diets of the mice, researchers were able to eliminate their stress behaviors.
Depression and Inflammation
Researchers at Imperial College London and University of South Carolina have identified a new culprit in depression: inflammation.
Inflammation produces histamine, which prompts the body to flood problem areas with immune cells. While this mechanism is beneficial for fighting infections, long-term inflammation can trigger depression and a host of other problems.
Not only is there a connection between inflammation and depression, the researchers found that people with both depression and severe inflammation are less likely to respond to selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed variety of antidepressants, which work by increasing the levels of serotonin in the brain.
To test the connection between inflammation and serotonin, researchers injected a group of mice with an inflammation-causing toxin, and a control group with saline. Serotonin levels in the brains of the toxin-injected mice dropped significantly within minutes of injection, while the saline-injected mice showed no change in serotonin levels.
When they looked at the effect more closely, they found that the inflammation triggered by the toxin in turn prompts the release of histamine in the brains of the mice, which inhibited the release of serotonin.
To try to counter the effects of the inflammation, the mice were given SSRIs, but they did not boost serotonin levels in the toxin-affected mice. Because the brains of humans have some of the same serotonin-related functions, the discovery might enable depression to be diagnosed and treated through the measurement of serotonin and histamine in human brains.
Recently, mouse studies involving hallucinations have shed some light on mental disorders that list hallucination as a symptom, including schizophrenia and psychosis.
According to a study published in the April 2 issue of Science, researchers at the Washington University School of Medicine in St. Louis developed a technique that induces sound hallucinations in mice, which could help scientists understand the brain circuits involved in schizophrenia and other disorders that cause hallucinations.
Because mice can’t let researchers know when they are hallucinating, the team came up with a way to detect when the mice were perceiving something that wasn't really there. They created a game where mice would try to detect a particular sound amid varying degrees of background noise, and were trained to expect a reward when they heard the sound.
Eventually, the mice were trying so hard to hear the sound that they sometimes “heard” it when it was not actually there. Because people are known to hallucinate more frequently when they expect to see or hear something, the researchers increased the frequency of the expected sound, which caused more false alarms in the mice.
These hallucination-like false perceptions were marked by an increase in the brain chemical dopamine, which made sense to the researchers because dopamine has already been linked to hallucinations, and some schizophrenia drugs block the effects of dopamine.
The team's success in better understanding exactly how dopamine is connected to hallucination, as well as how dopamine affects the brain processes surrounding hallucination, could lead to new treatment for mental illnesses marked by hallucination, such as schizophrenia and other psychotic disorders.
Schizophrenia, Autism and the Thalamus
Many mental disorders share similar symptoms, such as hallucination, attention deficits, cognitive impairment, and learning disabilities, so finding a way to treat a single symptom could lead to potential treatments for multiple conditions.
Now, a new study from MIT has uncovered a common cause for a type of cognitive impairment found in some people with autism and schizophrenia. By studying mice, the researchers found a similar dysfunction in a neural circuit in the thalamus, which plays a key role in cognitive tasks such as memory formation and learning. The dysfunction was caused by the absence or mutation of certain genes.
One of those genes is Ptchd1, an X-carried gene the absence of which can lead to attention deficits, hyperactivity, aggression, intellectual disability, and autism spectrum disorders in boys.
The researchers found that Ptchd1 loss affected two specific regions of the thalamus—the anterodorsal (AD) thalamus and the anteroventral (AV) thalamus. Circuits between the AD and AV thalamic regions and the retrosplenial cortex (RSC) were responsible for different types of memory formation.
When they suppressed the expression of Ptchd1 in the mice, researchers saw a marked decline in memory encoding. They repeated the experiment with four other genes, one linked with autism and three common in schizophrenics, and saw the same memory impairments.
The discovery could lead to the development of new treatments targeted to specific thalamic circuits, which could be effective for several different types of brain disorders.
As science increases its understanding of how mice brains and behavior can shed light on mental disorders in humans, researchers are optimistic that their work with mice will pave the way for better mental health in humans.