Discovering translational biomarkers in neurodevelopmental disorders.

Investment in drug development for neurodevelopmental disorders has suffered from recent failures in clinical trials that were based on promising preclinical findings. Here, we discuss development and validation of translational biomarkers of neurodevelopmental disorders that can enable more informative clinical experiments and translational success in these diseases.

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.

On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.

NINDS epilepsy and autism spectrum disorders workshop report.

The association of epilepsy and autism spectrum disorders (ASD), although well-recognized, is poorly understood. The purpose of this report is to summarize the discussion of a workshop sponsored by the National Institute of Neurological Disorders and Stroke, with support from the National Institute of Child Health and Human Development, Autism Speaks, and Citizens United for Research in Epilepsy, that took place in Bethesda, Maryland, on May 29 and 30, 2012. The goals of this workshop were to highlight the clinical and biological relationships between ASD and epilepsy, to determine both short- and long-term goals that address research and treatment conundrums in individuals with both ASD and epilepsy, and to identify resources that can further both clinical and basic research.

CoAIMs: a cost-effective panel of ancestry informative markers for determining continental origins.

Background: Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment.

Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression.

Serotonin (5-HT) has been proposed to promote neuronal plasticity during the treatment of mood and anxiety disorders and following neurodegenerative insult by altering the expression of critical genes including brain-derived neurotrophic factor (BDNF). In this study, mice with constitutive reductions in the serotonin transporter (SERT) or BDNF were investigated to further assess the functional relationship between serotonin neurotransmission and BDNF expression. Using a modified extraction procedure and a commercial enzyme-linked immunosorbant assay, 50% decreases in BDNF protein in hippocampus, frontal cortex and brain stem were confirmed in 4-month-old mice lacking one copy of the BDNF gene (BDNF(+/-)).

Brain-derived neurotrophic factor plays a critical role in contextual fear conditioning.

In this study, brain-derived neurotrophic factor (BDNF) heterozygous knock-outs were tested on fear conditioning, and their wild-type littermates were used as controls. Results showed that BDNF(+/-) mice are impaired in contextual learning, whereas tone learning remains intact. Because BDNF is involved in synaptic transmission and contextual learning is hippocampal dependent, we hypothesized that this deficit is attributable to abnormal BDNF-modulated synaptic plasticity in the hippocampus.

GAP-43 is critical for normal development of the serotonergic innervation in forebrain.

Serotonergic (5-HT) axons from the raphe nuclei are among the earliest afferents to innervate the developing forebrain. The present study examined whether GAP-43, a growth-associated protein expressed on growing 5-HT axons, is necessary for normal 5-HT axonal outgrowth and terminal arborization during the perinatal period. We found a nearly complete failure of 5-HT immunoreactive axons to innervate the cortex and hippocampus in GAP-43-null (GAP43-/-) mice.