Molecular pathways of anxiety revealed by knockout mice.
Anxiety is a normal reaction to threatening situations, and serves a physiological protective function. Pathological anxiety is characterized by a bias to interpret ambiguous situations as threatening, by avoidance of situations that are perceived to be harmful, and/or by exaggerated reactions to threat. Although much evidence indicates the involvement of the gamma-aminobutyric acid, serotonin, norepinephrine, dopamine, and neuropeptide transmitter systems in the pathophysiology of anxiety, little is known about how anxiety develops and what genetic/environmental factors underlie susceptibility to anxiety. Recently, inactivation of several genes, associated with either chemical communication between neurons or signaling within neurons, has been shown to give rise to anxiety-related behavior in knockout mice. Apart from confirming the involvement of serotonin, gamma-aminobutyric acid, and corticotrophin-releasing hormone as major mediators of anxiety and stress related behaviors, two novel groups of anxiety-relevant molecules have been revealed. The first group consists of neurotrophic-type molecules, such as interferon gamma, neural cell adhesion molecule, and midkine, which play important roles in neuronal development and cell-to-cell communication. The second group comprises regulators of intracellular signaling and gene expression, which emphasizes the importance of gene regulation in anxiety-related behaviors. Defects in these molecules are likely to contribute to the abnormal development and/or function of neuronal networks, which leads to the manifestation of anxiety disorders.
Wood
S J
SJ
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Toth
M
M
D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*