A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia
| Autor: | Seth G. N. Grant, Marcia Roy, Nathan G. Skene |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Life Sciences & Biomedicine - Other Topics Male INTELLECTUAL DISABILITY Disease Developmental psychology neuroscience Mice transcriptomics 0302 clinical medicine POSTSYNAPTIC DENSITY NMDA RECEPTORS Young adult Biology (General) Prefrontal cortex Child post-mortem GENE-EXPRESSION Neurons Sex Characteristics AGE-OF-ONSET General Neuroscience Brain BIPOLAR DISORDER General Medicine SIGNALING COMPLEXES Middle Aged 3. Good health Genomics and Evolutionary Biology Schizophrenia Child Preschool Medicine Female medicine.symptom Life Sciences & Biomedicine Neuroglia Research Article Sex characteristics Adult Adolescent QH301-705.5 DORSOLATERAL PREFRONTAL CORTEX Science Prefrontal Cortex Nerve Tissue Proteins Biology Affect (psychology) General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Young Adult Delusion medicine genomics Animals Humans human mouse Aged Science & Technology General Immunology and Microbiology Gene Expression Profiling evolutionary biology CORTICAL DEVELOPMENT Infant medicine.disease Mental health Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation DE-NOVO MUTATIONS Mutation Synapses Transcriptome 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 6 (2017) Skene, N G, Roy, M & Grant, S G N 2017, ' A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia ', eLIFE, vol. 6, e17915 . https://doi.org/10.7554/eLife.17915 eLife |
| Popis: | The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia. eLife digest In our lifetime, we go through many changes – physically and also intellectually. At certain ages, we are particularly vulnerable to develop psychiatric disorders, and the majority of mental conditions start to manifest in teenagers and young adults. The symptoms for schizophrenia, for example, a mental health disorder in which patients often experience hallucinations, delusion or changes in behavior, typically start in the mid-twenties. Schizophrenia tends to run in families and it is likely that different combinations of faulty genes that affect the connections between nerve cells increase the chance of having the disease. Until now, scientists have assumed that certain situations and environmental factors trigger the condition, but it was unknown if genes could influence the age at which the disease will begin. To explore whether genes in the brain change at certain time points, Skene et al. examined how the genes are turned on and off across the lifespan of healthy mice and humans. The results showed that in both mice and humans, a ‘genetic lifespan calendar’ controlled every cell type in the brain and directed the way they worked at different ages. The timing was so precise that it was possible tell the age of a mouse or a person simply by looking at the way the genes were expressed in a tissue sample. Skene et al. then studied how the genetic lifespan calendar controlled the genes damaged in schizophrenia, and found that the calendar caused a major reorganization of the genes at the time when the symptoms started. This suggests that the genetic lifespan calendar is a crucial factor that can determine at what age the disease will start. The next step will be to study how the genetic lifespan calendar programs changes throughout the brain and to explore if it could be manipulated to change how the brain ages. This could help to develop new types of treatments for schizophrenia and other conditions of the brain. |
| Databáze: | OpenAIRE |
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