Bechara Saab

Only 200 years ago, virtually nothing was known about the biological workings of the mind. Today, there is a deep (though far from complete) understanding of the cellular and molecular mechanisms underlying the encoding of memory, arguably the most fundamental aspect ...

Research in molecular biology often relies on parallel analysis of nucleic acids, protein and other molecules from a given tissue. When extracted from a single sample however, the quality and quantity of these products can be compromised. One solution is to obtain near-identical samples from multiple animals and dedicate each to a given molecular component, but this approach is not optimal from both an operational and ethical perspective. Thus, we refined the methods for cryohomogenization to allow efficient use of a single experimental sample so that it can easily be divided into fractions for extraction of different molecular components, immediately or after storage. Using western blot, nanodrop UV/V spectrometry, and a bioanalyzer, we show that cryohomogenized hippocampus samples provide high-quality RNA and protein without significant loss in abundance. The method may be particularly advantageous for parallel molecular extraction from brain structures with known hemispheric lateralization, such as the hippocampus, parietal cortex, suprachiasmatic nucleus, and amygdala.Copyright © 2013 Elsevier B.V. All rights reserved.

Exposure to stressful events can be differently perceived by individuals and can have persistent sequelae depending on the level of stress resilience or vulnerability of each person. The neural processes that underlie such clinically and socially important differences reside in the anatomical, functional, and molecular connectivity of the brain. Recent work has provided novel insight into some of the involved biological mechanisms that promises to help prevent and treat stress-related disorders. In this review, we focus on causal and mechanistic evidence implicating altered functions and connectivity of the neuroendocrine system, and of hippocampal, cortical, reward, and serotonergic circuits in the establishment and the maintenance of stress resilience and vulnerability. We also touch upon recent findings suggesting a role for epigenetic mechanisms and neurogenesis in these processes and briefly discuss promising avenues of future investigation.Copyright © 2012 Elsevier Inc. All rights reserved.

MicroRNAs (miRNAs) are a class of short non-coding RNAs that primarily regulate protein synthesis through reversible translational repression or mRNA degradation. MiRNAs can act by translational control of transcription factors or via direct action on the chromatin, and thereby contribute to the non-genetic control of gene-environment interactions. MiRNAs that regulate components of pathways required for learning and memory further modulate the influence of epigenetics on cognition in the normal and diseased brain. This review summarizes recent data exemplifying the known roles of miRNAs in memory formation in different model organisms, and describes how neuronal plasticity regulates miRNA biogenesis, activity and degradation. It also examines the relevance of miRNAs for memory impairment in human, using recent clinical observations related to neurodevelopmental and neurodegenerative diseases, and discusses the potential mechanisms by which these miRNAs may contribute to memory disorders. This article is part of the Special Issue entitled 'Neuroepigenetic Disorders'.

There is strong evidence that the epigenetic regulation of gene transcription, by way of covalent modifications of DNA and DNA-associated proteins, and through microRNAs, is an essential process underlying neuronal plasticity and memory. This chapter brings the non-specialist reader up to speed on important concepts within memory research, focusing on the role of the hippocampus, the molecular regulation of synaptic strength, and the behavioral tools used to examine learning and memory in experimental animals. Next, we describe the close association that is observed between defective epigentic processes and impaired memory in several cognitive diseases. The bulk of the chapter is then devoted to describing three broad classes of technical approaches that have been used to better understand how DNA methylation, histone post-translational modification, and microRNAs might contribute to memory. We end the chapter with a discussion on the potential relevance of epigenetic processes in sustaining memory traces in the brain over very long periods of time.

Epigenetic marks in mammals are essential to properly control the activity of the genome. They are dynamically regulated during development and adulthood, and can be modulated by environmental factors throughout life. Changes in the epigenetic profile of a cell can be positive and favor the expression of advantageous genes such as those linked to cell signaling and tumor suppression. However, they can also be detrimental and alter the functions of important genes, thereby leading to disease. Recent evidence has further highlighted that some epigenetic marks can be maintained across meiosis and be transmitted to the subsequent generation to reprogram developmental and cellular features. This short review describes current knowledge on the potential impact of epigenetic processes activated by environmental factors on the inheritance of neurobiological disease risk. In addition, the potential adaptive value of epigenetic inheritance, and relevant current and future questions are discussed.

In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and ...