Depression May Not Be All in Your Head
Repeated social defeat stress (when an intruder mouse is repeatedly threatened by a larger mouse defending its home territory) is often used as a model to study human depression. Animals repeatedly exposed to social defeat stress start to exhibit depression-like behaviors such as social avoidance and loss of interest in sucrose. Georgia Hodes, a researcher at Mount Sinai School of Medicine, reported at a recent scientific meeting that repeated defeat stress–induced behavior was blocked when IL-6, an inflammatory cytokine released by white blood cells in the blood, was inhibited. The central nervous system did not appear to be involved.
Interestingly, mice with more white blood cells and more IL-6 release at baseline (prior to the social defeat stress) were more likely to show the defeat-stress depressive behaviors.
Editor’s Note: The higher number and greater reactivity of white blood cells seen in these mice could be a clinical marker of vulnerability to defeat stress, and such findings are worthy of study in human depression. White blood cells are critical to fighting infection and sometimes their overactivity can contribute to inflammation. In meta-analyses, a subgroup of depressed patients consistently show elevated inflammatory markers (including IL-1, IL-6, TNF alpha, and CRP), and it remains to be seen whether these markers of inflammation are generated in the central nervous system or come from white blood cells in the blood, and whether their targeted suppression could be a new route to antidepressant effects (as in the study of defeat stress in mice).
Information from Environmental Experiences Can Be Passed on in Dad’s Sperm
Contrary to all common sense, researcher Brian Dias showed that when rats that were future fathers learned to associate an odor with a shock, this learning could be passed on to the next generation when the father mated with a female rat that had not learned the same association.
It turns out that the next generation of rat pups shows increased behavioral reactivity to the odor in a process different from the fear conditioning they might exhibit if they learned to avoid the odor through their own experiences.
Presumably, the pup is somehow programmed through an epigenetic modification of the father’s sperm to grow more neurons from the nose to the olfactory bulb that specifically react to the odor its father feared, and not to other odors. Miraculously, when the second generation pup grows up and fathers a third generation pup, the new pup also shows increased behavioral sensitivity to that specific odor. How the odor information from the first generation is represented in the fathers’ sperm and passed on to their descendants is still a complete mystery.
There are also new data that a father rat fed a diet deficient in folic acid (vitamin B9) will sire offspring with more congenital malformations. Additionally, an obese father rat fed a diet that includes extra fat calories will sire pups that become obese as adults even when fed a normal milk diet from a svelte mother before weaning and then fed a normal diet after weaning.
Mothers’ behavior usually gets most of the credit and/or blame for her children’s behavior, but now it looks like fathers’ diet or behavior (even before they have children) may have lasting consequences for their offspring.
Conditioned Fear Can Be Transmitted Transgenerationally in Rodents
Scientists often use fear conditioning to study rodents’ learning and behavior. If a particular stimulus (such as a light, a sound, or an odor) is presented paired with the delivery of a mild shock, the animal begins to associate the stimulus with the shock and will freeze when it is presented and avoid the stimulus.
New research shows that if a pregnant rat (known as a dam) goes through fear conditioning that pairs an odor with a shock, the rat’s offspring will also avoid that odor into adolescence. Even if the pups are raised by a different mother who never went through the fear conditioning, they still avoid the odor into adolescence, showing that they do not learn the behavior through watching their mother.
The conditioning is specific to the particular odor, such that a different odor not used in the fear conditioning does not evoke a heightened reaction from the pups. It appears that the pup learns the fear through chemical signals, such as alarm pheromones that can pass through the placenta.
Rats Learn Fear Conditioning From One Another
Rats who are taught to associate a light with an electric shock learn to avoid the light. This process is known as conditioned fear. New research shows that if one rat watches another rat go through fear conditioning, the observing rat will also show the effects of fear conditioning. It will also avoid the light, but only if it had previous experience with fear conditioning. It appears that rats have the ability to learn from other rats’ painful experiences.