Astrocytes Become Reactive with Normal Aging

What's the science?

Astrocytes are are the most abundant cell in the brain. They help to respond to injury and are important for maintaining overall brain health by supporting neurons, recycling neurotransmitters and regulating the formation and elimination of the connections between neurons. Astrocyte dysfunction is known to play a role in neurodegenerative diseases, but how astrocytes change throughout normal aging is not well known. One way to understand these changes is by looking at the transcription of genes in astrocytes. This week in PNAS, Clarke and colleagues performed RNA sequencing in mice at different stages of life to understand how astrocytes change over time.

How did they do it?

RNA sequencing was performed in mice at five time points between adolescence and old age, in three different brain areas: the cortex, hippocampus (involved in memory), and striatum (involved in movement and reward). They validated their findings using fluorescence in situ hybridization and quantitative polymerase chain reaction (qPCR) techniques (these techniques can confirm gene expression changes). To investigate whether the resident immune cells of the brain - microglia - play a role in inducing changes in astrocytes with aging, they compared astrocyte gene expression in mice with and without (knock-out mice) cytokines. Cytokines are released by microglia in response to neuroinflammation. 

What did they find?

Using RNA sequencing, they found that as astrocytes age, they are more likely to express genes associated with reactivity (this is when astrocytes become dysfunctional -- typically associated with neuroinflammation). Astrocytes were especially likely to become reactive in the hippocampus and striatum, which are areas particularly susceptible to neurodegeneration in aging. Using qPCR, a method used to observe DNA sequences, they found that reactive gene expression was not increased in the knock-out mice without cytokines, indicating that microglia expression of cytokines may be partially responsible for changes in astrocyte gene expression. Aged brains also formed many more reactive astrocytes in response to the neuroinflammation inducer ‘lipopolysaccharide’, which may indicate vulnerability of the aged brain to disease and inflammation.

                       Microglia & Astrocytes,  S  ervier Medical Art,  image by BrainPost,  CC BY-SA 3.0

                       Microglia & Astrocytes, Servier Medical Art, image by BrainPost, CC BY-SA 3.0

What's the impact?

This is the first study to demonstrate that astrocytes become reactive as they age and that microglia- the immune cells of the brain- may be responsible through cytokine activity. More reactive astrocytes were found in brain regions vulnerable to degeneration, suggesting that changes in astrocyte gene expression may help explain neurodegenerative diseases or cognitive decline in aging.

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Reach out to study author Dr. Laura E. Clarke on Twitter@ClarkeLauraE

Clarke et al., Normal aging induces A1-like astrocyte reactivity. (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

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.

 

The Nature vs. Nurture of Song Learning

What's the Science?

Learning is affected by individual genetic differences and previous experience. The way that genetics and experience interact to affect learning is not fully understood. This week in PNASMets and colleagues set out to determine whether song learning by birds is influenced by genetics and whether quality of instruction has any impact on this genetic influence.

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How did they do it?

To test whether genetics has an impact on learning, they performed an experiment where birds (finches) from different genetic backgrounds learned a song tempo after receiving computer instruction. To see whether the quality of instruction changes the influence of genetics on learning, a second set of birds received enriched instruction (tutoring by other birds).

What did they find?

They found that the birds with different genetic backgrounds and the same level of experience produced songs with a range of different tempos. This shows that genetics alone has a strong impact on learning song tempo. When they factored in the quality of instruction, they found that the genetic influence on learning became weaker, meaning that experience also has a strong impact on learning and can even override the impact of genetics. 

What's the Impact?

This is one of the first studies to test the contribution of genetics and experience on learning. Importantly, this study highlights that the influence of genetics on learning can depend a lot on our experience. Rather than ‘Nature vs. Nurture’, learning seems to be all about the interaction between the two.
 

Read the original journal article here.
 

D. G. Mets, M. S. Brainard, Genetic variation interacts with experience to determine interindividual differences in learned song. Proc. Natl. Acad. Sci. 115, 421–426 (2017).