By Angharad Brewer Gillham, Frontiers science writer

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How mice and rats help study depression

Mice and rats are key model animals that help us understand how depression works and how to treat it. A huge number of people around the world live with this devastating disorder, but its causes and symptoms are so varied that it is hard to test new treatments and to reproduce experiments to prove those treatments work. Scientists writing in Frontiers in Behavioral Neuroscience reviewed the evidence for rodent models of depression and found that models imitating social stress or a disrupted early life have had some success.

Meanwhile, models with behavioral stressors designed to induce helplessness are easily compared to other labs’ work but aren’t complex enough to model depression. A key element of depression is anhedonia, struggling to enjoy life, but this is extremely difficult to model in nonhuman animals. The most popular options available test preference for sweet tastes.

The team concluded that the best option is to provide mice with a more naturalistic setting to live in, with more space to socialize and to follow their own inclinations. This helps avoid experimenter influence and allows spontaneous behavior from the mice to be monitored and interpreted, and creates a more effective mimic of depressive behavior when the setting is manipulated. These settings are more expensive and harder to reproduce across labs, but they offer an important ray of hope for scientists trying to develop new treatments for depression.

Article link: https://www.frontiersin.org/articles/10.3389/fnbeh.2021.811987/full

My family and other animals: how tracking pedigrees helps study heredity

A team of Italian scientists has developed a method for tracking epigenetic effects across generations. The scientists, who were studying dopamine transporters, realized that they needed a new method to track their complex experiments and took inspiration from Gregor Mendel’s famous experiments on heredity.

The tracker they developed allowed them to investigate behavioral changes in rats and figure out whether they had an epigenetic basis or were caused by the previous generation providing different maternal care because their dopamine transporters didn’t function properly. After careful study, they realized that the behavioral changes they were seeing were caused by nature rather than nurture, but also that the effect of the allele responsible varied based on the parent it was inherited from. Rats inheriting the allele from their mother were restless and seemed to have trouble falling asleep.

Epigenetics is a rapidly developing field, and the extent of transgenerational effects on inheritance is just beginning to be explored. The authors hope to use this simple and practical method of recording to clarify the effects of epigenetics on human and animal disorders.

Article link: https://www.frontiersin.org/articles/10.3389/fnbeh.2021.781235/full

Are Alzheimer’s mouse models too specialized?

Scientists use mouse models to reproduce Alzheimer’s-related pathologies that we see in humans, try to understand how they happened, and find future treatments. But, asked Dr Martine Ammassari-Teule, are the models too specialized to reflect humans who develop Alzheimer’s spontaneously?

In order to model pathologies, populations of mice have to be inbred. Since they don’t display normal genetic variation, they can’t be representative of a normal population. Inserting a mutated gene to try to understand genetic effects on the pathologies modeled by a strain can mean losing the controlled variables that make comparisons between experiments possible. It is also difficult to compare different inbred strains with characteristics relevant to a research question, because they have cognitive differences that mean the same experiments may have different impacts on them.

Ammassari-Teule set out a definition for the kind of mice that we need to study Alzheimer’s: animals with a memory that dangerous mutations can impact measurably and that shows cognitive decline before the controls begin to experience normal age-related degeneration. She predicted that increasing genetic diversity in the mice used for experiments will be the answer to modeling human populations, but beware – careful characterization will be required to make sure controls are equivalent.

Article link: https://www.frontiersin.org/articles/10.3389/fnbeh.2022.868473/full

How scientists can use neuroscience to fight mental health stigma

Behavioral neuroscientists writing in the Horizons in Behavioral Neuroscience Research Topic have laid out a bold path towards leveraging neuroscience to eliminate the stigma of mental health. While there is no direct evidence for neural hardwiring of stigma, stigma is deeply rooted in our emotions and the neural basis for it could throw light on the feed-backward and feed-forward loops that regulate the way humans think, feel, and act.

Ignorance worsens stigma, the authors pointed out, but information doesn’t improve it. Understanding that mental illness has a biological basis can induce less blame, but it doesn’t stop people treating those who are mentally ill poorly. The stigma against poor mental health in itself compromises medical care for many conditions globally. While educational initiatives are valuable, they need to be properly assessed to ensure their effectiveness and investigate their effect on the neurobiological underpinnings of stigma.

The scientists suggested that research and communication should be focused on understanding the plasticity of the brain and the neural basis of stigma, and finding ways to change the perceptions that lead to it. “If stigma involves learning and memory,” they asked, “can at least some of its components be erased?”

Article link: https://www.frontiersin.org/articles/10.3389/fnbeh.2021.812184/full

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