Boost Your Cognitive Ability By Protecting Your Dopamine Neurons (LMX1A)

The LMX1A gene codes for a protein called LIM homeobox transcription factor 1-alpha. This gene and its protein play different roles at different stages of life.

In early development — meaning before birth, and during the first few months of life —  the LMX1A gene stimulates the growth dopamine neurons in the developing brain [R, R, R].

In other words, how active this gene is when your brain is just starting to grow essentially determines how many dopamine neurons you will have later on in life!

Although its role in creating neurons is already finished by early childhood, LMX1A continues to play an important role throughout adulthood and later life by protecting your dopamine neurons from oxidative stress and mitochondrial dysfunction. This helps keep neurons healthy, which supports overall cognitive function [R].

The activity of the LMX1A gene early in your life determines how many dopamine neurons you will eventually have — and later on, it helps keep these neurons alive and healthy by protecting them against damage and stress.

The LMX1A gene is important for cognitive function because dopamine — and the neurons that produce and secrete it — are vital for several key aspects of cognitive function, such as working memory and cognitive flexibility [R, R].

When it comes to protecting these dopamine neurons, this gene primarily affects the efficiency of your cell’s energy-producing mitochondria. Low levels of LMX1A cause mitochondria to become “tired out” more easily when your cells need a lot of energy — and when your mitochondria have to work harder, they produce significantly more reactive oxygen species (ROS), the cellular waste products that cause oxidative stress [R, R].

If ROS levels get high enough, they can overwhelm your neurons’ natural antioxidant defenses, resulting in cellular damage or even cell death. Although this is bad news for any cell in your brain, oxidative stress is especially dangerous to dopamine neurons, due to their generally higher levels of activity compared to other types of neurons [R, R].

Therefore, having adequate LMX1A gene activity is very important for making sure that your dopamine neurons aren’t being constantly stressed out and damaged! This is probably why SNPs in the LMX1A gene have been associated with many different important aspects of cognitive function such as learning, multiple different types of memory, and even overall intelligence (IQ) [R, R, R].

Dopamine neurons are some of the more delicate types of neurons you have in your brain — and the LMX1A gene plays a crucial role in keeping them healthy, thereby supporting optimal cognitive function.

You can see your genotype for the LMX1A SNP rs11809911 in the table below:

The two possible alleles for this SNP are ‘C’ (major) and ‘T’ (minor). When it comes to optimal cognitive function, it’s better to have the ‘CC’ genotype (which about 35% of people have).

For example, a gene-targeted study in 218 participants found that the ‘T’ allele was associated with reduced performance on a wide variety of cognitive tests, including tests of learning and memory, cognitive flexibility (executive function and attention), processing speed, and even general intelligence (IQ) [R].

Although this particular study only reported this effect for bipolar patients, this result also agrees with several other studies linking risk factors in the LMX1A gene to differences in cognitive performance among otherwise healthy people.

For example, people with better-functioning copies of this gene show enhanced performance on tests of working memory, and also achieve higher levels of improvement in their working memory after going through cognitive training programs [R]!

This result is particularly interesting, as working memory is one of the cognitive functions most strongly associated with dopamine. In fact, the authors of this study concluded that these cognitive benefits were most likely due to higher number of dopamine neurons in the beneficial LMX1A genotype group — which fits very well with what we know about the general role of this gene in the brain [R, R, R].

Finally, LMX1A risk factors have also been linked with increased risk of developing schizophrenia and Parkinson’s disease — two disorders which not only involve cognitive deficits, but which are also directly caused by the dysfunction or widespread loss of dopamine neurons, specifically [R, R].

Taking all these findings into consideration, it is likely that people with the ‘CC’ genotype for this LMX1A SNP have a copy of this gene that is more active, which in turn helps them maintain a larger number of healthy dopamine neurons. In contrast, the ‘T’ allele likely causes the LMX1A gene to work less efficiently, which impairs cognitive performance by causing dopamine neurons to be more vulnerable to stress, cell damage, and even death.

People with the ‘CC’ genotype for rs11809911 show enhanced cognitive performance, likely because their version of the LMX1A gene is more active. In contrast, carriers of the ‘T’ allele likely have a less effective version of this gene, making their dopamine neurons more vulnerable to stress and damage.