Abstract

Growth factors play important roles in synapse formation. Mouse models of neuropsychiatric diseases suggest that defects in synaptogenic growth factors, their receptors, and signaling pathways can lead to disordered neural development and various behavioral phenotypes, including anxiety, memory problems, and social deficits. Genetic association studies in humans have found evidence for similar relationships between growth factor signaling pathways and neuropsychiatric phenotypes. Accumulating data suggest that dysfunction in neuronal circuitry, caused by defects in growth factor-mediated synapse formation, contributes to the susceptibility to multiple neuropsychiatric diseases, including epilepsy, autism, and disorders of thought and mood (e.g., schizophrenia and bipolar disorder, respectively). In this review, we will focus on how specific synaptogenic growth factors and their downstream signaling pathways might be involved in the development of neuropsychiatric diseases.

Highlights

  • Neuropsychiatric diseases are increasingly recognized to have developmental origins

  • DIRECTIONS Growth factor signaling between pre- and postsynaptic neurons is critical for proper connections between individual neurons, and for the development of appropriate brain circuitry

  • Synaptogenic growth factors play a key role in ensuring that synapses develop properly and are modulated appropriately over time, so that suitable emotional and behavioral responses to the environment are generated when necessary

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Summary

SYNAPTIC NEUROSCIENCE

The best-laid plans go oft awry: synaptogenic growth factor signaling in neuropsychiatric disease. Mouse models of neuropsychiatric diseases suggest that defects in synaptogenic growth factors, their receptors, and signaling pathways can lead to disordered neural development and various behavioral phenotypes, including anxiety, memory problems, and social deficits. Genetic association studies in humans have found evidence for similar relationships between growth factor signaling pathways and neuropsychiatric phenotypes. Accumulating data suggest that dysfunction in neuronal circuitry, caused by defects in growth factor-mediated synapse formation, contributes to the susceptibility to multiple neuropsychiatric diseases, including epilepsy, autism, and disorders of thought and mood (e.g., schizophrenia and bipolar disorder, respectively). We will focus on how specific synaptogenic growth factors and their downstream signaling pathways might be involved in the development of neuropsychiatric diseases

INTRODUCTION
Synaptogenic signaling in neuropsychiatric disease
None identified Haploinsufficiency
Multiple loss of function mutations Knockout
Apoptosis of neurons
None identified
Hypomorphic alleles in compound heterozygotes Knockout
Hypomorphic mutation in EGFR
Heterozygous mutations
Direct infusion of GDNF to ventral tegmental area
Viral transduction RNAi knockdown
Findings
CONCLUSIONS AND FUTURE DIRECTIONS
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