TY - JOUR
T1 - Cellular Plasticity Cascades
T2 - Genes-To-Behavior Pathways in Animal Models of Bipolar Disorder
AU - Einat, Haim
AU - Manji, Husseini K.
N1 - Funding Information:
We acknowledge the support of the Intramural Program of the National Institute of Mental Heath and the Stanley Medical Research Institute. HE is a recipient of the National Alliance for Research on Schizophrenia and Depression 2005 Young Investigator Award. Owing to space limitations, we often cited review articles and apologize to those authors whose original data could not be included.
PY - 2006/6/15
Y1 - 2006/6/15
N2 - Background: Despite extensive research, the molecular/cellular underpinnings of bipolar disorder (BD) remain to be fully elucidated. Recent data has demonstrated that mood stabilizers exert major effects on signaling that regulate cellular plasticity; however, a direct extrapolation to mechanisms of disease demands proof that manipulation of candidate genes, proteins, or pathways result in relevant behavioral changes. Methods: We critique and evaluate the behavioral changes induced by manipulation of cellular plasticity cascades implicated in BD. Results: Not surprisingly, the behavioral data suggest that several important signaling molecules might play important roles in mediating facets of the complex symptomatology of BD. Notably, the protein kinase C and extracellular signal-regulated kinase cascades might play important roles in the antimanic effects of mood stabilizers, whereas glycogen synthase kinase (GSK)-3 might mediate facets of lithium's antimanic/antidepressant actions. Glucocorticoid receptor (GR) modulation also seems to be capable to inducing affective-like changes observed in mood disorders. And Bcl-2, amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, and inositol homeostasis represent important pharmacological targets for mood stabilizers, but additional behavioral research is needed to more fully delineate their behavioral effects. Conclusions: Behavioral data support the notion that regulation of cellular plasticity is involved in affective-like behavioral changes observed in BD. These findings are leading to the development of novel therapeutics for this devastating illness.
AB - Background: Despite extensive research, the molecular/cellular underpinnings of bipolar disorder (BD) remain to be fully elucidated. Recent data has demonstrated that mood stabilizers exert major effects on signaling that regulate cellular plasticity; however, a direct extrapolation to mechanisms of disease demands proof that manipulation of candidate genes, proteins, or pathways result in relevant behavioral changes. Methods: We critique and evaluate the behavioral changes induced by manipulation of cellular plasticity cascades implicated in BD. Results: Not surprisingly, the behavioral data suggest that several important signaling molecules might play important roles in mediating facets of the complex symptomatology of BD. Notably, the protein kinase C and extracellular signal-regulated kinase cascades might play important roles in the antimanic effects of mood stabilizers, whereas glycogen synthase kinase (GSK)-3 might mediate facets of lithium's antimanic/antidepressant actions. Glucocorticoid receptor (GR) modulation also seems to be capable to inducing affective-like changes observed in mood disorders. And Bcl-2, amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, and inositol homeostasis represent important pharmacological targets for mood stabilizers, but additional behavioral research is needed to more fully delineate their behavioral effects. Conclusions: Behavioral data support the notion that regulation of cellular plasticity is involved in affective-like behavioral changes observed in BD. These findings are leading to the development of novel therapeutics for this devastating illness.
KW - Mania
KW - cellular plasticity
KW - underlying mechanisms
UR - http://www.scopus.com/inward/record.url?scp=33745468256&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2005.11.004
DO - 10.1016/j.biopsych.2005.11.004
M3 - Review article
C2 - 16457783
AN - SCOPUS:33745468256
SN - 0006-3223
VL - 59
SP - 1160
EP - 1171
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 12
ER -
