Scientists find gender-distinct circuit for depression
October 9, 2019
Science Daily/Michigan State University
Depression affects women nearly twice as much as men, but unraveling the brain's blueprint that regulates this behavior, let alone identifying specific molecular differences between sexes, has proven difficult.
Michigan State University researchers, however, have found and flipped a switch in the brain, revealing a single circuit in mice that activates during stress and is controlled by testosterone. The results, published in Biological Psychiatry, focus on the activity between neurons in the ventral hippocampus, which become active under stress and emotion, and their activation of nucleus accumbens neurons, critical players in reward and motivation.
"What makes these findings stand out is not only identifying this new circuit," said A.J. Robison, MSU physiologist and lead author of the study, "but also observing and confirming how it drives different behaviors in males and females."
Oddly enough, many circuit-specific animal model studies involving depression-related behaviors don't include female subjects. This gap exists despite sex differences in several depression-related brain regions, including the hippocampus, Robison added.
To help close this void, Robison and a team of MSU scientists focused on this hippocampus-accumbens circuit and saw that the activity in male brains during stress was significantly lower than in females, and this required testosterone. When they removed testosterone, however, the male mice began expressing depression-like behaviors.
Conversely, the team observed increased circuit activity in female brains, but when testosterone was introduced, the neurons quieted, and the female mice became resistant to the depression-like behaviors.
"Even with our best antidepressants, such as Prozac, we don't know exactly how they work," Robison said. "This is the first time we've found a circuit that drives this sexually different behavior; other scientists can now explore how this could translate to identifying new therapeutic targets in humans."
Robison's group used chemogenetic tools to manipulate specific circuit activity in the mouse brain in this study. Such tools may inform the development of "genetic medicine" for the treatment of human diseases in the future.
https://www.sciencedaily.com/releases/2019/10/191009132324.htm
University of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth
October 16, 2005
Science Daily/University of Saskatchewan
A synthetic substance similar to ones found in marijuana stimulates cell growth in regions of the brain associated with anxiety and depression, pointing the way for new treatments for these diseases, according to University of Saskatchewan medical research published today in The Journal of Clinical Investigation.
Xia Zhang, an associate professor in the U of S neuropsychiatry research unit, led the team that tested the effects of HU-210, a potent synthetic cannabinoid similar to a group of compounds found in marijuana. The synthetic version is about 100 times as powerful as THC, the compound responsible for the high experienced by recreational users.
The team found that rats treated with HU-210 on a regular basis showed neurogenesis – the growth of new brain cells in the hippocampus. This region of the brain is associated with learning and memory, as well as anxiety and depression.
The effect is the opposite of most legal and illicit drugs such as alcohol, nicotine, heroin, and cocaine.
“Most ‘drugs of abuse’ suppress neurogenesis,” Zhang says. “Only marijuana promotes neurogenesis.”
Current theory states that depression may be sparked when too few new brain cells are grown in the hippocampus. It is unclear whether anxiety is part of this process, but if true, HU-210 could offer a treatment for both mood disorders by stimulating the growth of new brain cells.
But Zhang cautions that HU-210 is only one of many cannabinoids. His previous work with marijuana shows that while the plant may contain medicinal compounds, they come in the same package as those that cause symptoms such as acute memory impairment, addiction, and withdrawal. Also, the HU-210 used in the study is highly purified.
“This is a very potent cannabinoid oil,” Zhang says. “It’s not something that would be available on the street.”
Marijuana has been used for recreational and medicinal purposes for centuries, evoking public interest and controversy along the way. As a medicine, the plant is used to ease pain in multiple sclerosis patients, combat nausea in cancer patients, and stimulate appetite in people afflicted with AIDS. It has also been used to treat epilepsy and stroke.
Zhang’s work is the latest product of the U of S Neural Systems and Plasticity Research Group (http://www.usask.ca/neuralsystems/group.htm), a multidisciplinary effort by researchers from the Colleges of Arts and Science, Engineering, Kinesiology, Medicine, Pharmacy and Nutrition, and Veterinary Medicine. The group collaborates to study the function of neural systems, from nerves to brain, in living organisms. In particular, they look at how these systems change over time with experience.
Zhang’s research is supported by a grant from the Canadian Institutes of Health Research (CIHR), as well as a CIHR New Investigator Award. The Saskatchewan Health Research Foundation provided funding support to establish the Neural Systems and Plasticity Research Group, as well as post-doctoral fellowship awards to research team members Wen Jiang and Shao-Ping Ji.
https://www.sciencedaily.com/releases/2005/10/051016083817.htm