- A research done on male mice shows obesity affects brainpower.
- The main reason of obesity-associated cognitive degradation is microglia (immune cells).
- Excessive microglia in obese mice destroys dendritic spines, affecting the performance of thinking.
More than 2 billion people in the world are either overweight or obese – Institute for Health Metrics and Evaluation report. The peak of obesity rates is shifting towards adults in developed countries. The highest proportion (13%) of obese people live in the U.S, while India and China together account for 15% of the world’s obese population.
Obesity is a serious issue: it’s a chronic disease that raises the risk of developing conditions like type 2 diabetes, heart disease, bone and joint disease, etc. It’s also linked to cognitive degradation, and higher possibilities of developing brain-related disorders, including dementia, later in life.
Recently, scientists shed light on how obesity affects the brain. Studies done in the last few couple of years suggest microglia (immune cells in the central nervous system) is the main culprit. In obese people, active microglia destroys dendritic spines that create synapses, declining cognitive ability. The new research provides a solid evidence supporting this notion.
The Experiment
To examine the cellular mechanism responsible for cognitive decline associated with obesity, researchers observed diet-induced obesity in male mice. Like humans, mice that consume lots of fat rapidly gain weight. Within 3 months of heavy-fat diet, mice gained 40% more weight than those who were given standard diet.
Neuroscientists at Princeton University carefully observed the behavior of obese mice. They were worse at remembering location of a particular object and escaping mazes, showing signals of declined brainpower.
Typically, microscopic knobs named dendritic spines receive inputs from a single axon at the synapse. These spines play a crucial role in maintaining synaptic strength and transmitting electrical signals to the neurons’ cell body.
Reference: JNeurosci | doi:10.1523/JNEUROSCI.0789-18.2018
Compared to normal mice, researchers found fewer dendritic spines in different parts of the obese mice’s hippocampi – brain structures crucial for consolidating information from short-term memory to long-term memory, and for spatial memory that enables navigation.
The main reason behind the destruction of these dendritic spines is microglia. A large quantity of active microglia is lurked among sparse nerve cell connections in obese mice.
An obese mouse had fewer dendritic spines (arrows, bottom) than a normal mouse (top) | Courtesy of researchers
To confirm this, researchers tweaked microglia in obese mice. As expected, this helped them preserve dendritic spines, and the thinking-performance of mice improved gradually. In other words, they successfully showed that pharmacological inhibition of microglia immune cells in obese mice prevented both dendritic spin loss and cognitive decline.
What’s Next?
The study clearly shows that microglia immune cells degrade memory and learning process through phagocytosis of synapses that are crucial for optimal function. Thus, it is possible to treat the detrimental effects of obesity by influencing microglial activation.
So far, they have conducted experiments with male mice, so it would be intriguing to see if female obese mice show the same behavior. It is necessary to address them because hippocampus synaptic density alters throughout the ovarian cycle.
Read: Eating In 10-Hour Window Can Prevent Obesity and Metabolic Syndrome
In the future, researchers will analyze whether the effects of obesity on the brain can be prevented by obstructing signaling mechanisms in body fat.
