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Review
. 2012 Oct 4;76(1):160-74.
doi: 10.1016/j.neuron.2012.08.037.

The fibroblast growth factor family: neuromodulation of affective behavior

Cortney A Turner  1 , Stanley J Watson, Huda Akil
Affiliations
Review

The fibroblast growth factor family: neuromodulation of affective behavior

Cortney A Turner et al. Neuron. .

Abstract

In this review, we propose a broader view of the role of the fibroblast growth factor (FGF) family in modulating brain function. We suggest that some of the FGF ligands together with the FGF receptors are altered in individuals with affective disorder and modulate emotionality in animal models. Thus, we propose that members of the FGF family may be genetic predisposing factors for anxiety, depression, or substance abuse; that they play a key organizing role during early development but continue to play a central role in neuroplasticity in adulthood; and that they work not only over extended time frames, but also via rapid signaling mechanisms, allowing them to exert an "on-line" influence on behavior. Therefore, the FGF family appears to be a prototype of "switch genes" that are endowed with organizational and modulatory properties across the lifespan, and that may represent molecular candidates as biomarkers and treatment targets for affective and addictive disorders.

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Figures

Figure 1
Figure 1. The Role of FGF2 in the Vulnerability to Mood and Addictive Disorders
Panel A depicts the major factors that converge on the brain to modify vulnerability to complex behavioral disorders such as major depression or substance abuse- Genes, Development, Stress and other Environmental Events all converge at the level of the brain to alter neural circuits that control behavior. Moreover, the behavior itself, such as a depressive episode or a period of substance abuse, in turn modifies the brain through neuroplasticity mechanisms, and increases the likelihood of relapse. Panel B illustrates the fact that FGF2 has been implicated in each of these mechanisms, with specific examples of its role in each of these domains. Thus, FGF2 plays multiple roles— genetic, developmental, and experiential, in regulating the propensity to certain behaviors such as mood disorders or drug abuse. In general, low FGF2 levels predispose towards depression, while high FGF2 levels predispose towards substance abuse.
Figure 2
Figure 2. FGF signaling can have functional effects through different mechanisms in multiple time domains
Panel A shows that FGF ligands can interact with FGF membrane receptors on both neurons and glial cells. Intracellular FGF ligands can also interact with voltage-gated sodium channels (VGSC), particularly near the initial axon segment. Moreover, FGF receptors can have partners, e.g. they can interact with neural cell adhesion molecules such as NCAM, and can heterodimerize with G Protein Coupled Receptors such as the 5-HT1A receptor. These events take place in neurons and glia, and trigger a host of signaling pathways, with multiple function consequences. Panel B: depicts the various classes of functional changes in the brain that can be triggered by the actions of FGF signaling. Panel C: depicts the behavioral and clinical outcomes of the neural mechanisms triggered by FGF signaling and underscores the multiple time domains in which they can occur, from altering lifelong patterns of behavior (through modifying temperamental predisposition and coping styles) to sustained changes during a given period of the organism's life (e.g. an episode of depression) to ongoing regulation of motivated and affective behavior.
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