UNews - Jamshid Faraji

Male experimenters make female rats uneasy

caroline.zentner — Tue, 06 Sep 2022 20:00:30 +0000

Researchers at the ��Ѹ��Դ��߿�Ƭ of Lethbridge’s Canadian Centre for Behavioural Neuroscience (CCBN) have shown that the sex of an experimenter, a factor typically not accounted for in preclinical studies using rodents, could have an effect on study results. Their findings were recently published in Frontiers in Neuroscience.

Drs. Gerlinde Metz and Jamshid Faraji say study results call for improved standards.

Dr. Gerlinde Metz, along with Drs. Mirela Ambeskovic, Jamshid Faraji and others, compared the effects of male and female experimenters on male and female rats. In some situations, the experimenter was physically present and in others, unwashed T-shirts worn by the experimenters were placed in the room. Animals were handled by their male or female experimenters for five minutes a day for 10 days before any experimental manipulations were done to ensure the rats were used to the experimenters.

“We watched a lot of different variables and compared how the animals responded to a male and a female experimenter working with them,” says Metz. “We saw that the presence of a human makes a huge difference and we saw again that the rats responded to the T-shirt. It’s not only visual interaction the rats responded to, but also some olfactory cues that influenced their behaviour.”

Researchers measured the rats’ stress levels before and after they were subjected to a mildly stressful situation. Infrared thermography was used to detect skin temperature and blood samples were taken to determine the levels of hormones involved in the stress response (corticosterone and oxytocin). Female rats in the presence of a male experimenter or T-shirt worn by a male experimenter showed higher levels of corticosterone and lower levels of oxytocin, the so-called bonding hormone. They also responded to the presence of a male experimenter by displaying more anxiety-like behaviour, such as spending more time near the walls of their enclosure, and had higher body surface temperatures.

“An interesting finding is that female rats display these heightened stress responses even after frequent exposure to male experimenters,” says Faraji. “We call it the male observer effect.”

“It’s really a very important finding because it will affect how we design experiments,” says Metz. “I don’t mean we should only have female experimenters work with rats or any laboratory animals, but we need to report it and have better standards of how we pursue research with laboratory animals. We also need to be aware that our presence and our handling affects them.”

The findings may help explain the replication crisis, which occurs when the same experiments done at different labs produce different results. When a study’s results can’t be replicated from one lab to another, the credibility of the findings can be in doubt.

“All scientists are concerned about controlling unwanted factors when they are manipulating experimental variables,” says Faraji. “These results address this concern and reveal one of these factors in the field.”

Given the study results, Metz says it would be better to have a series of observations or tests and then take an average or, as Faraji suggests might be possible in the future, to eliminate the variable by using robotics. The ultimate goal is to ensure results obtained in the preclinical stages are reliable and will lead to successful clinical trials in humans. Rodents are often used in preclinical studies, which take place before any testing in humans is done, to determine if a drug, treatment or procedure might be useful.

“Because experimenter sex in animal studies is not commonly reported, improved standards should require researchers to report the sex of experimenters,” says Metz. “We cannot avoid the presence of a human experimenter or handling the animals in many situations, but we need to be aware of these variables and maybe include appropriate control situations in an experiment to be sure about the results.”

Perhaps the study results aren’t surprising to pet owners, who can attest to the bonds they have with their pets. One study, referred to in an article in Smithsonian Magazine, explored the bond between humans and their dog companions and found that dogs and humans gazing into each other’s eyes caused both to secrete oxytocin.

Study examines importance of social interaction on brain health in wake of pandemic isolation

trevor.kenney — Mon, 27 Jun 2022 22:02:46 +0000

As society begins to emerge from the restrictions of the COVID-19 pandemic, social interaction is beginning to return and according to a new study out of the ��Ѹ��Դ��߿�Ƭ of Lethbridge — that couldn’t come soon enough.

Drs. Jamshid Faraji, left, and Gerlinde Metz.

Drs. Gerlinde Metz and Jamshid Faraji (Canadian Centre for Behavioural Neuroscience) wanted to know how important social interaction is and how it affects the brain when such opportunities are limited. They led a group of researchers in examining the effect that physical and social enrichment had on the expression of oxytocin and brain-derived neurotrophic factor (BDNF).

“We showed in 2018 that social support is particularly impactful on females and their mental health,” says Metz of their studies in rodent models. “We also discovered that social support helps with longevity and can actually slow down biological aging. We focused on oxytocin levels in the brain because it is the bonding hormone that downregulates stress.”

This new study seeks to understand the mechanism behind how oxytocin works.

“This is particularly important now because we realized the critical role of social support and loneliness and mental health during the pandemic amid the heightened levels of stress and anxiety specifically among pregnant mothers,” adds Metz. “The stress we experience now has potentially transgenerational consequences and may be passed down to offspring three or four generations down the road. We want to understand what we can do to mitigate the effects of that stress and to do so, we need to understand how stress affects the brain.”

The research group focused on the relationship between oxytocin and BDNF, which is the most abundant neurotrophic factor in the nervous system — what Metz refers to as the fountain of youth.

“BDNF actually leads to better learning, better mental health, brain development and healthy aging — it’s really beneficial in every way,” she says. “It acts on brain function throughout our lifespan and even enhances the survival of neurons and regeneration of neurons in the brain.”

In their study, Faraji injected an antagonist that blocked the effects of oxytocin. Without oxytocin interaction, BDNF expression was severely reduced, denying the brain of all those beneficial effects. To follow the dominos, lack of social interaction leads to less oxytocin which leads to lower BDNF expression.

“This was a causal link that we’d been missing before,” explains Metz.

They also discovered over the course of their work that while physical and social enrichment benefits both males and females and having both is best, physical interaction was most important to males and social interaction resonated much more with females.

“We have to be careful when we look at animal research and compare it to humans but I think we can learn some good lessons from these studies,” says Metz. “Right now, our population faces a severe mental health crisis and is aging rapidly. Pregnant mothers and elderly are especially vulnerable, and they feel the hit of the pandemic and the effects of social distancing. Given the links between social isolation, stress and health, it is more apparent now than ever to offer social support to vulnerable individuals or marginalized populations.”

While the pandemic has brought these concerns to the forefront, the lessons continue with those populations who traditionally have experienced social isolation. Metz also expresses hope because their work has shown how the brain incredibly heals itself over time given the right stimulus.

“I think it really helps us to understand these biological mechanisms because they give us something to work with, variables we can measure,” she says. “We can then see how treatments or interventions are successful and make adjustments where needed to better help people.”

The study — Regional Differences in BDNF Expression and Behavior as a Function of Sex and Enrichment Type: Oxytocin Matters — is published in Oxford Academic.

U of L researchers demonstrate the importance of studying sex differences

caroline.zentner — Wed, 03 Jun 2020 16:51:46 +0000

In the past, many scientific research studies focused on using only male subjects, whether in human or animal experiments. Now researchers like Drs. Jamshid Faraji and Gerlinde Metz at the ��Ѹ��Դ��߿�Ƭ of Lethbridge’s Canadian Centre for Behavioural Neuroscience are shining a spotlight on biological sex differences and making them an integral part of their research.

“It’s a big issue,” says Faraji. “Researchers and scientists have to consider males and females, particularly in relation to stress. The results could be misleading if we don’t consider the psychological differences between males and females.”

Dr. Jamshid Faraji

In their recent study, published in Frontiers in Behavioral Neuroscience, Faraji and Metz developed an animal model that demonstrates sex differences in the thermal response to stress.

While fever is typically produced as a result of infection, a condition in humans called psychogenic hyperthermia results in increased body temperature due to chronic stress. The condition affects more females than males and often occurs in adolescence.

“Young females are known to experience high raises in temperature in response to stress,” says Metz. “Their core body temperature can go up to 41 degrees. There’s not a good animal model and, if you want to understand the mechanisms, it’s helpful to see if this also works in animals. This study is the first observation of psychogenic regulation of temperature in mice. No one has shown that before.”

Faraji and Metz found that the skin temperature of female rats was significantly higher than in male rats when they experienced a specific kind of stress.

The researchers subjected male and female mice to two types of stress. In one condition, mice were individually placed into transparent Plexiglas tubes that kept them standing still in a vertical position. In the other, the mice were placed in a white plastic tube that mimicked the natural burrow of a mouse. The tunnel allowed the mice to freely move and turn around, but prevented them from standing on their hind limbs. Mice engage in rearing behaviour, or standing on their hind limbs, to explore and investigate their environment. Before the mice experienced any stress, the researchers monitored the rearing behaviour of the mice during free exploration and found that females reared more often than males during active hours.

Dr. Gerlinde Metz

Following both stress conditions, the researchers took blood samples to measure levels of stress hormones.

“While we expected differences, both males and females showed the same flight or fight response to being deprived of some of their natural physical activity,” says Faraji.

The researchers then went a step further and used an infrared thermal imaging camera that detects changes in skin temperature. That’s where the differences showed up.

“Our results showed significant differences between males and females only when they were deprived of rearing behaviour,” says Faraji. “Female mice showed an increase in temperature while males did not. This shows that males and females respond differently to certain kinds of stress.”

Having established an animal model allows researchers to do further work on exploring the thermal regulation systems in males and females, which could one day lead to a better understanding of the same mechanisms in humans.

For Metz, the experiment has parallels to the current restrictions placed on movement because of the COVID-19 pandemic.

“Having their movements curtailed is stressful for mice and humans, too,” says Metz. “Being largely confined to our houses during the lockdown and, even though we can still physically move about, may be experienced as stressful.”

In response to such prolonged stress, people often develop psychosomatic symptoms or mental health issues like depression and anxiety. Health authorities around the world have responded by increasing supports for mental health treatment.

“This study is a great example of how the brain can control our body functions,” says Metz. “The brain is the master gland and it can direct many physical responses to our environment and to our experiences. It shows how much the mindset determines general health and symptoms. We have to look at the whole body in terms of well-being.”

UNews - Jamshid Faraji

Male experimenters make female rats uneasy

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