Plasticity in Neural Genomes During Early Life Experiences

What's the science?

The brain undergoes changes (i.e. plasticity) during early development, and these are thought to be due to gene-environment interactions. Retrotransposons are segments of DNA that are mobile and can essentially “jump” and insert themselves throughout the genome, and could be one way that DNA is modified by interactions with the environment. Currently, we don’t know whether retrotransposons play a role in changing DNA during early life. This week in Science, Bedrosian and colleagues observe the effects of early maternal care on retrotransposon levels in mouse DNA.

How did they do it?

Mice were divided into two groups: high and low maternal care (as evidenced by median natural levels of grooming and nursing over 2 weeks). They used droplet digital Polymerase Chain Reaction (ddPCR) to quantify the number of retrotransposons (‘L1’ retrotransposons, making up 17% of the mouse genome) in mice DNA from brain (hippocampus and frontal cortex) and heart tissue between the high and low care groups. They also manipulated the level of maternal care to test how this affected the number of retrotransposons over time.

What did they find?

There were more retrotransposons in the hippocampus in mice with low maternal care (but not in the heart or frontal cortex). When they manipulated the levels of maternal care by separating the mother and pup, retrotransposon levels also varied. They then tested what causes retrotransposon levels to change. They measured neurogenesis (the formation of new neurons) by staining hippocampal neurons, and found no differences (i.e. neurogenesis was not responsible for changes in retrotransposon levels). They also used bisulfite sequencing to measure the level of methylation of DNA (a DNA modification that affects gene expression). The retrotransposon regions in hippocampal DNA showed less methylation in mice with low maternal care (who have higher retrotransposon levels), suggesting that methylation is responsible for changes in retrotransposon levels with maternal care.

What's the impact?

This is the first study to show that maternal care alters retrotransposon (i.e. jumping gene) activity in early life. Before, we did not understand exactly how early life experience can change the structure of DNA. Now we know that retrotransposons are one of the ways that DNA plasticity (i.e. changes) occurs in response to early life experiences.

T. Bedrosian et al., Early life experience drives structural variation of neural genomes in mice. Science (2018). Access the original scientific publication here.

The Role of White Matter Connections in Adolescent Mental Health and Cognition

What's the science?

The brain’s white matter pathways connect many different regions of the brain, and these connections undergo immense change during adolescence. Psychiatric disorders or their symptoms (e.g. anxiety, depression, obsessive-compulsive disorder, attention deficit hyperactivity disorder, post-traumatic stress disorder) often develop during this time. This week in JAMA Psychiatry, Alnaes and colleagues report that cognition and psychopathology symptoms are related to the brain’s connections in the frontal lobe.

How did they do it?

6487 adolescents (without a diagnosed mental disorder) completed 1) reports on a wide variety of clinical /psychopathological symptoms, and 2) cognitive tests. Of these adolescents, 748 had MRI scans of the brain’s white matter connections, and 2946 had genetic testing done. They assessed whether psychopathological symptoms and cognitive scores were heritable (ie. genetically inherited) and whether these scores were related to brain connectivity patterns. They then used a robust technique called machine learning to test relationships, meaning they ensured that the proposed model of the relationship between the brain and cognition/psychopathy was accurate in multiple different subgroups of participants.

What did they find?

Weaker connections in two of the brain’s white matter tracts (uncinate fasciculus and inferior fronto-occipital fasciculus) were associated with lower cognitive scores, and a greater number of psychopathological symptoms. Anxiety, antisocial behaviour, and psychosis were correlated with these connections. Genetic variance explained 18% of an individual’s cognitive score and 16% of their general psychopathy score.

William Hirstein. Diagram by Katie Reinecke., White matter fiber tracts, colour by BrainPost, CC BY 3.0

What's the impact?

This study found that psychopathological symptoms in adolescents and lower cognitive scores were predicted by lower connectivity in pathways of the brain’s frontal lobe. These pathways connect the frontal lobe with other regions known to be involved in emotion and cognition. Lower connectivity in frontal white matter pathways could play a role in the development of psychiatric disorders in youth.

D. Alnaes et al., Association of Heritable Cognitive Ability and Psychopathology With White Matter Properties in Children and Adolescents. JAMA Psychiatry. (2018) Access the original scientific publication here.