Repetitive behavior disorders are relatively common. One of the best known in this family is obsessive compulsive disorder, or OCD, which affects more than 2 percent of the U.S. population. Existing treatments, often medications, may not bring adequate relief for about half of those with the disorder.
The researchers have uncovered some of the basic brain mechanisms behind repetitive behavior, which may ultimately lead to new ways to treat psychiatric disorders, including OCD, at their root.
The team focused on a type of brain cell called astrocytes, which are largely thought of as support cells, though much of their role in regulating neurons — and behavior — has remained uncharted. They developed a method to dial down astrocyte calcium signals in the mouse brain. They created a variant of a pump, dubbed CalEx, which significantly reduced calcium elevations inside the cell. The team focused on an area of the brain called the striatum, known to be involved in movement and brain disorders.
After treating healthy mice, they observed the behavior of the animals, and immediately saw a difference: When placed in an open arena, the treated mice spent significantly more time in the corners. The authors first attributed this to anxiety or to a motor control problem, but these mice performed just as well as untreated animals in tests of motor control and measures of anxiety.
When the researchers looked more closely, however, they saw that the animals were actually grooming themselves — excessively. Their bouts of self-grooming were 450 percent longer than controls.
“For months, we wondered why they spent so much time in corners,” said, the study’s first author. “It turned out that they were spending a lot of time self-grooming. This phenotype resembled very closely repetitive behaviors in humans; for example, the repetitive hand washing that happens with some OCD patients.”
When the team reduced calcium signaling in other areas of the brain, the mice didn’t exhibit the OCD-like behaviors, suggesting the striatum is key. That finding corroborated earlier evidence that the striatum controls self-grooming.
Using a variety of tests to look at the different levels of function, from molecular to neurocircuitry, the team determined that astrocytes were regulating the activity of nearby nerve cells, by altering levels of the neurotransmitter GABA in the striatum.
“Over a decade ago, researchers had found that in humans, the early stages of Huntington’s disease often are marked by obsessive-compulsive-like symptoms,” the lead author said. “We wanted to see if the underlying mechanism also had anything to do with astrocyte calcium signaling.”
They found that when they gave mice with early Huntington-like symptoms a compound to block a key step in the calcium signaling process, the mice stopped their OCD-like self-grooming behaviors. Huntington’s disease is a progressive movement disorder involving the breakdown of cells in the brain.
Researchers didn’t expect to find psychiatric effects associated with astrocyte calcium signaling. “The fact that we could observe psychiatric-related phenotypes after astrocyte-specific manipulations was unexpected and hence a very pleasant surprise,” the senior author said. “As far as I know, this is the first demonstration that astrocytes can regulate an innate behavior and it opens the door for exploiting them for therapies aimed at mental illness.”
A key contribution of the new study is the lab’s development of a novel method of silencing calcium signaling within specific circuits of the brain. The existing method is to knock out the molecules completely, across the whole brain and the whole lifespan. But that method has not so far produced any clear changes in behavior, as the current study did.
The results may pave the way for the development of novel treatments for OCD, the researchers said.
“Many patients are non-responsive or partially responsive to the current available treatment options,” the senior author said. “Our findings point to a new direction for potential therapy development by revealing an involvement of astrocytes in repetitive behaviors that are related to OCD.”
The team hope their findings may also help lead to development of new therapies for other psychiatric disorders.
https://www.uclahealth.org/brains-support-cells-may-play-a-central-role-in-repetitive-behaviors-related-to-ocd
https://www.cell.com/neuron/fulltext/S0896-6273(18)30688-3
Astrocytes play a central role in repetitive behaviors related to OCD
- 1,581 views
- Added
Edited
Latest News
Alzheimer's disease symptom…
By newseditor
Posted 27 Jun
Gene-regulatory networks in…
By newseditor
Posted 27 Jun
How apoE influences Aβ aggr…
By newseditor
Posted 26 Jun
How do plants break down da…
By newseditor
Posted 26 Jun
A new tool for neurological…
By newseditor
Posted 26 Jun
Other Top Stories
Cancer cells in cerebrospinal fluid hijack iron to survive
Read more
Skin cancer diagnosis using human-AI collaboration!
Read more
Treating EGFR inhibitor resistant lung tumors with low does of 4 drugs
Read more
Proteogenomic Signatures of Non-smoking Lung Cancer are Different!
Read more
Detection of kidney cancer using plasma and urine cell-free DNA met…
Read more
Protocols
BicemuS: A new tool for neu…
By newseditor
Posted 26 Jun
Deciphering spatial domains…
By newseditor
Posted 23 Jun
High-throughput volumetric…
By newseditor
Posted 21 Jun
Bioengineered human colon o…
By newseditor
Posted 14 Jun
Development of an efficient…
By newseditor
Posted 12 Jun
Publications
Immunometabolism in atheros…
By newseditor
Posted 27 Jun
Long-range inhibitory neuro…
By newseditor
Posted 27 Jun
The microtubule-dynamin bin…
By newseditor
Posted 27 Jun
High sugar diet-induced fat…
By newseditor
Posted 27 Jun
Brain repair mechanisms aft…
By newseditor
Posted 27 Jun
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar