Study at Mumbai institute: Use more female animal specimens in labs for balanced findings

Researchers should include more female animal specimens in laboratory experiment if they want to avoid skewed results, according to a study by a three-member team at the Tata Institute of Fundamental Research (TIFR).

The study stated that a female brain processes stressful situations differently than a male one. The researchers said pre-clinical research in laboratories globally has largely focussed on male specimens, especially for stress-related disorders such as anxiety and depression which are higher among women, while substance abuse is more among men.

Researchers observed that study results are important because there are sexually dimorphic rates among humans for stress-related disorders and substance abuse. Sexual dimorphism is a condition where the two sexes of the same species exhibit different characteristics beyond the differences in sexual organs. “Though cultural factors do play a key role, we found that the way neuronal circuits in the brain are processing acute stressors is different between males and females,” said Vidita Vaidya, neuroscientist at the department of biological sciences, TIFR. “Studying only the male brain, therefore, gives only a partial insight. It is a serious problem to keep using the male prototype even for studying disorders.”

Experts who were not connected to the study said the findings were important because the sexes behave differently in similar situations. “This kind of knowledge is key to preventing and treating post-traumatic stress disorder, which is more common in women. Very few researchers compare multiple stressors, especially in both sexes, so it also contributes to a fundamental understanding of traditional models used in animal research,” said Rebecca M Shansky, associate professor (laboratory of neuroanatomy and behaviour) at the department of psychology in Northeastern University, Boston.

Differences in the stress processing circuitry in the male and female brain could also involve different therapeutic approaches and clinical treatments for both sexes, said researchers.

Shansky, whose laboratory has been studying both sexes since 2011, said, “Many researchers don’t use female animals because they mistakenly believe that circulating ovarian hormones will interfere with their “real” data. The reality is that variability in data from male and females is the same, and that variability in females cannot always be attributed to hormones.”

In the TIFR study, male and female rats were put through two stressful situations — one in a cramped space and other in water. Tests were then conducted to observe neural activation patterns within stress-responsive regions of the brain — in the hypothalamus and amygdala, primary circuits that respond to stress, and the prefrontal cortex and hippocampus, which process stress.

The hypothalamus controls hormonal release, while the amygdala processes fear as a rapid response to stress that helps in adapting to the situation. Results showed that the number of neurons, which got activated in these regions of the brain, was identical in both rats for the two stressors.

The male-female difference, however, came to the fore in the higher order stress processing circuitry — the prefrontal cortex is the decision making circuitry, and the hippocampus which provides information for context, memories and recalling experiences. The number of neurons that got strongly activated in the prefrontal cortex and the hippocampus in cramped conditions was more among male rats. But number of neurons that got switched on in the prefrontal cortex and the hippocampus when swimming in water was more among female rats.

“If we had stopped the experiment after the first response, we too would have generalised the results for both sexes. Therefore, how stress is processed in terms of the interpretation and long term consequences is likely to be different between the male and female brain,” said Vaidya. It’s therefore important what and where one is looking.”

The study was published in the international journal Stress this month.