Epigenetics: The Future of Psychology & Neuroscience. Richard E. Brown Psychology Department Dalhousie University Halifax, NS, B3H 4J1

Transcription

1 Epigenetics: The Future of Psychology & Neuroscience Richard E. Brown Psychology Department Dalhousie University Halifax, NS, B3H 4J1

2 Nature versus Nurture Despite the belief that the Nature vs. Nurture argument about the causes of neurobehavioral phenomena is dead (Traynor & Singleton, 2010) it persists in many areas of Psychology and Neuroscience. Indeed, the nature vs. nurture issue seems alive in discussions of development, athletic ability, neural disorders, aging, etc.

3 The Central Dogma of Molecular Biology (F. Crick, 1970, Nature, 227, ) Transcription of DNA to RNA protein: This dogma forms the backbone of molecular biology and is represented by four major stages. 1. The DNA replicates its information in a process that involves many enzymes: replication. 2. The DNA codes for the production of messenger RNA (mrna) during transcription. 3. In eukaryotic cells, the mrna is processed (essentially by splicing) and migrates from the nucleus to the cytoplasm. 4. Messenger RNA carries coded information to ribosomes. The ribosomes read this information and use it for protein synthesis. This process is called translation. Proteins do not code for the production of protein, RNA or DNA. They are involved in almost all biological activities, structural or enzymatic.

4 The central dogma of molecular biology: what about and the environment? Behaviour Genetics and The Central Dogma Genes Brain Behaviour Altered Genes Altered Brain BUT What about environmental influences? Brain Altered Behaviour Genes?? Environment Behaviour? Genes x Environment Brain Behaviour

5 Genes & environment interact True, the old dogma of nature versus nurture is dead, but unfortunately it has been replaced by a puzzle even harder to solve. (Traynor & Singleton, 2010, p.199) The solution to the nature versus nurture problem has been to propose that genes and behavior interact in the determination of neural and behavioral development (Hebb, 1953; Dowling, 2004). Hebb, D.O. (1953). British Journal of AnimalBehaviour 1: Heredity and Environment in Mammalian Behaviour D.O. Hebb McGill University, Montreal, Canada

6 Environmental enrichment facilitates neural development.

7 Epigenetic processes provide a mechanism for environmental factors to modulate gene activity. C. D. Allis, T. Jenuwein, D. Reinberg, M.-L. Caparros (Eds). Epigenetics. CSHL Press, Ch.3, p29 Genetic mutations of the DNA template are heritable somatically and through the germ line. Epigenetic variations in chromatin structure modulate the use of the genome by: (1) Histone modifications (mod) (2) Chromatin remodeling (remodeler) (3) Histone variant composition (yellow nucleosome) (4) DNA methylation (Me) and (5) Noncoding RNAs. Marks on the chromatin template may be heritable through cell division and collectively contribute to determining cellular phenotype.

8 Neurochemical signaling mechanisms regulate chromatin. Coordinated Modification of Chromatin. The transition of a naïve chromatin template to active euchromatin (left) or the establishment of repressive heterochromatin (right), involving a series of coordinated chromatin modifications. In the case of transcriptional activation, this is accompanied by the action of nucleosome-remodeling complexes and the replacement of core histones with histone variants (yellow, namely H3.3). (Figure 11, Allis et al., 2007)

9 Changes from active to silent chromatin states as the result of feedback loops between intermediate states. (A) Different chromatin states. Both DNA and histone modifications interact to determine whether genes are active or silent. Transcriptional activators or repressors also determine whether genes are activated or repressed. (B) For example, histone H3K9 when acetylated via HAT (histone acetyltransferase) activates genes, but when deacetylated, or methylated, or when CpG methylation occurs, then gene repression (silencing) occurs. Environmental stimuli (light, temperature), diet, hormones and diseases such as cancer can act as epigenetic factors to regulate gene activation and gene silencing.

10 How do epigenetic processes integrate environmental and genetic information? Big Questions in Epigenetic Research. The many experimental systems used in epigenetic research have unveiled numerous pathways and novel insights into the mechanisms of epigenetic control. Many questions, as show in the figure, still remain and require further elucidation or substantiation in new and existing model systems and methods. (From: Allis et al., 2007, Ch 3, p.55)

11 Epigenetics, Psychology and Neuroscience Early studies by Meaney showed that maternal behavior is an epigenetic mechanism in development.

12 Epigenetic mechanisms are involved in learning and memory.

13 Epigenetic mechanisms function in all areas of neuroscience, including neural development, the neural basis of learning and memory, drug addiction, sexual differentiation of brain and behavior, aging and neurodegeneration and psychiatric disorders.

14 Neural development Learning & Memory

15 Drug Addiction Sexual differentiation

16 Aging Neurodegeneration

17 Psychiatric disorders

18 Epigenetic mechanisms are involved in all areas of psychology: developmental, social, cognition, learning and memory, aging, and clinical. Developmental Social Cognitive

19 Age-related learning & memory loss

20 Clinical disorders

21 Epigenetics as a unifying principle in psychology and neuroscience.

22 Behaviour The New Central Dogma Environment Neurochemistry (Extra- and intra-cellular) Epigenetic mechanisms DNA mrna Protein Synthesis Brain Development

23 Conclusions Epigenetic mechanisms are central to the understanding of brain-behavior relationships. Epigenetic mechanisms can form unifying principles linking diverse areas of psychology and neuroscience; from neuro-behavioral development through social, cognitive, clinical and aging mechanisms. Epigenetic mechanisms may provide new theories for diagnosing or treating neuro-behavioral and psychological disorders, such as schizophrenia, autism, depression and Alzheimer s disease. Epigenetics should form a central principle in the teaching of psychology and neuroscience.