Epigenetic mechanisms in psychiatric disorders
Although changes in genes are involved in psychiatric disorders, it is now increasingly accepted that many changes in gene expression in these disorders don’t stem from polymorphism in the DNA.
Rather, gene transcription is regulated by remodeling of chromatin structure via epigenetic processes. Chromatin is formed by a DNA molecule wrapped around an octomer of histones. Chromatin condensation and decondensation repress or enable, respectively, the accessibility of gene promoters to the transcriptional machinery, and the activity of transcription factors. The most significant epigenetic mechanisms are histone acetylation, which leads to chromatin relaxation that enables transcription, and DNA methylation, which occurs on specific cytosine-guanine dinucleotide domains (CpG islands) within gene promoters, and is associated with repression of transcription.
This project aims to characterize the role of epigenetic processes in psychiatric disorders such as schizophrenia and substance addiction.
Relapse prevention by memory erasure
Alcoholism is a chronic relapsing disorder, has severe impacts on society, and is responsible for 4% of death world-wide. By combining animal models and studies with alcoholic patients, this project focuses on preventing alcohol craving and relapse in abstinent subjects, by disrupting alcohol-associated memories that cause relapse to alcohol seeking and drinking.
It is increasingly accepted that memories become labile and erasable soon after their retrieval, during a memory reconsolidation process that depends on protein synthesis. We are looking into the molecular mechanisms that underlie reconsolidation of alcohol-associated memories, with the aim of disrupting the memories and preventing relapse to alcoholism. We are also developing in the lab behavioral treatments that will prevent relapse by disrupting memory reconsolidation.
Growth factors in addiction
Growth factors have a broad spectrum of functions in the development and maintenance of the nervous system. Abnormal function or expression of several growth factors has been implicated in various neuropsychiatric diseases.
Chronic exposure to excessive quantities of alcohol or other drugs of abuse lead to alterations in the nervous system (neuroadaptation) that promote the development of addiction phenotypes. Such neuroadaptations include alteration of the growth factors systems (e.g. Brain Derived Neurotropic Factor, BDNF; and Glial Cell Line-Derived Neurotropic Factor, GDNF), leading to transition from moderate and controlled alcohol consumption to excessive, out-of-control alcohol intake.
We are studying the role of these and other growth factors in the development of addiction, and in the aberrant learning and memory processes that are involved in addiction.