BMP Antagonist Gremlin 2 Regulates Hippocampal Neurogenesis and Is Associated with Seizure Susceptibility and Anxiety.

The Bone Morphogenetic Protein (BMP) signaling pathway is vital in neural progenitor cell proliferation, specification, and differentiation. The BMP signaling antagonist Gremlin 2 (Grem2) is the most potent natural inhibitor of BMP expressed in the adult brain; however its function remains unknown. To address this knowledge gap, we have analyzed mice lacking Grem2 via homologous recombination ( ).

Locus-Specific DNA Methylation Assays to Study Glutamate Receptor Regulation.

Recent findings indicate that glutamate receptors are regulated at the epigenetic level through the posttranslational modification of histones and through DNA methylation. Furthermore, dysregulation of these marks in the context of neurological disease has been shown to influence glutamate receptor function. Over the past two decades, an appreciation for the essential role epigenetic mechanisms play in nervous system function has led to the development of many methods and tools to map, quantitate, and manipulate these chromatin marks.

Lithium-Responsive Seizure-Like Hyperexcitability Is Caused by a Mutation in the Voltage-Gated Sodium Channel Gene .

() is an X-linked dominant mutation in identified more than 40 years ago. A previous study showed that caused spontaneous tremors and defects in reactive climbing behavior, and that these phenotypes were significantly suppressed when mutants were fed food containing lithium, a mood stabilizer used in the treatment of bipolar disorder (Williamson, 1982). This unique observation suggested that the mutation affects genes involved in lithium-responsive neurobiological processes.

Tet1 Oxidase Regulates Neuronal Gene Transcription, Active DNA Hydroxy-methylation, Object Location Memory, and Threat Recognition Memory.

A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this equilibrium remain elusive. Tet1 oxidase has been shown to play a key role in the active DNA demethylation in the CNS.

TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation.

Dynamic changes in 5-methylcytosine (5mC) have been implicated in the regulation of gene expression critical for consolidation of memory. However, little is known about how these changes in 5mC are regulated in the adult brain. The enzyme methylcytosine dioxygenase TET1 (TET1) has been shown to promote active DNA demethylation in the nervous system.

Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD.

Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by intrusive and persistent memories of a psychologically traumatic event that leads to significant functional and social impairment in affected individuals. The molecular bases underlying persistent outcomes of a transient traumatic event have remained elusive for many years, but recent studies in rodents have implicated epigenetic modifications of chromatin structure and DNA methylation as fundamental mechanisms for the induction and stabilization of fear memory. In addition to mediating adaptations to traumatic events that ultimately cause PTSD, epigenetic mechanisms are also involved in establishing individual differences in PTSD risk and resilience by mediating long-lasting effects of genes and early environment on adult function and behavior.