Astrocytes could play a key role in regulating ADHD

According to a new UCLA study, astrocytes, thought to provide primarily neuron-feeding and maintenance functions, could play a key role in the regulation of attention deficit disorder and l & # 39; hyperactivity.

"Unveiling how astrocytes contribute to brain function is one of the most important open questions in neuroscience. We have made progress, but our previous work did not tell us why increased calcium signaling by astrocytes – a communication method commonly used by astrocytes and neurons – would affect the neurons and neural circuits in which they reside. We decided to tackle this problem »

The study leader, Baljit Khakh, professor of physiology and neurobiology at the David Geffen School of Medicine at the University of California at Los Angeles (UCLA).

A chance discovery

Last year, Khakh's team showed that astrocyte regulation of neurons in a part of the brain called the striatum influenced repetitive behaviors such as those observed in obsessive-compulsive disorder, or OCD. The new study made a fortuitous discovery about how astrocyte signaling in the striatum – which plays a role in motor movement, cognition, and decision making – also affects ADHD-like behaviors.

Previous studies on human brain imaging had suggested that the striatum was involved in Attention Deficit Hyperactivity Disorder, among a number of other psychiatric disorders.

In the new study, the team used a method that increases the calcium signals of astrocytes in mice. Stratum astrocytes from adult mice were "infected" with a particular type of receptor.

The team administered a compound to stimulate the receptor, which ultimately led to an increase in the calcium level of the astrocytes.

To observe the impact of this change on the behavior of the animals, each animal was placed in an empty arena and allowed to explore. The treated mice were more active and traveled significantly greater distances than the untreated mice.

Disturbed attention

Although the authors first attributed the increase in activity to changes in motor control, the treated mice behaved just as well as animals not treated in motor tests. When the team took a closer look at the behavior of the mice, she found that the treated animals also exhibited an apparent lack of attention in certain behavioral tasks.

"For a while, we wondered why treated mice sometimes did not work well in simple tasks. It turned out that they were displaying disturbed attention. Mice did not pay attention to changes in ambient light levels and new objects, unlike normal mice. We think this may reflect attention-deficit hyperactivity behaviors,

said Jun Nagai, lead author of the study and postdoctoral researcher in Khakh's laboratory.

Astrocyte Synaptogenic Indices

Then, the team wanted to better understand what molecular changes could occur to alter the activity of neurons – and therefore rodents. With the help of a combination of techniques, the researchers found that the cascade of events actually began with the release of the neurotransmitter GABA by the striatal neurons, which resulted in an increased rate of calcium in astrocytes.

They showed that this increase in calcium alters the expression of a gene called Thbs1.

"The discovery that it was possible to observe psychiatry-related behaviors after triggering astrocyte-specific signaling was somewhat unexpected," Khakh explains. "In parallel with the work we published last year on the role of astrocytes in [obsessive compulsive disorder], our current results suggest that astrocytes can modify neurons to generate complex traits and behavioral characteristics. We think this means that ultimately, astrocytes could be exploited to treat behaviors badociated with mental illness. "

Khakh and his team plan to continue to explore astrocytes in brain function in the coming years, particularly with regard to the potential impact of their activity on other types of psychiatric disorders.

Jun Nagai, Abha K. Rajbhandari, Mohitkumar R. Gangwani, Ayaka Hachisuka, Giovanni Coppola, Sotiris C. Masmanidis, Michael S. Fanselow, Baljit S. Khakh
Hyperactivity with disturbed attention by the activation of a synaptogenic signal of astrocytes
Cell (2019). DOI: 10.1016 / j.cell.2019.03.019

Image: Yirui Sun, Wellcome Images