Cellular Plasticity Cascades: Genes-To-Behavior Pathways in Animal Models of Bipolar Disorder

  title={Cellular Plasticity Cascades: Genes-To-Behavior Pathways in Animal Models of Bipolar Disorder},
  author={Haim Einat and Husseini K. Manji},
  journal={Biological Psychiatry},
  • H. Einat, H. Manji
  • Published 15 June 2006
  • Biology, Psychology
  • Biological Psychiatry
Lithium: Neurotransmission and Cellular Mechanism Pathways Underlying Neuroprogression in Bipolar Disorder
This chapter reviews the therapeutic effects of lithium on neurotransmission and cellular signal transduction mechanisms underlying neuroprogression in bipolar disorder and key glycogen synthase kinase-3β-mediated mechanisms are highlighted, as they appear pivotal to therapeutic response.
Intracellular Signalling Pathways and Mood Disorders ( signalling pathways / mood disorders / antidepressants / mood stabilizers )
New neurochemical hypotheses of mood disorders are disclosed; they were formulated on the basis of known effects of antidepressants or mood stabilizers on intracellular signal transduction on the function, plasticity and survival of neurons.
A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?
Emerging data from preclinical and clinical research suggest an imbalance of the PKC signaling system in mood disorders, and PKC may be a critical molecular target for the development of innovative therapeutics.
Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats
Behavioral effects of Bcl-2 deficiency: implications for affective disorders.
The relationship between Bcl-2 and behavior is explored using mice with a targeted mutation but with a different background strain than previously tested, and the current lack of effect on anxiety measures may be related to high baseline anxiety of WTanimals.
Protein Kinase C Inhibition by Tamoxifen Antagonizes Manic-Like Behavior in Rats: Implications for the Development of Novel Therapeutics for Bipolar Disorder
The results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD and may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder.
Reverse translational strategies for developing animal models of bipolar disorder
These studies demonstrate that the use of ‘reverse translation’, drawing on patient-based findings to develop suitable animal models for BD, is useful, viable and deserves attention in new efforts to generate animal models of BD.


Molecular mechanisms underlying mood stabilization in manic-depressive illness: the phenotype challenge.
Direct evidence that the genes identified thus far are responsible for phenotypic changes associated with chronic lithium treatment is still lacking, so the combination of sensitive molecular technologies, appropriately designed paradigms, better behavioral analysis, and a chronobiologic approach seems necessary for the future identification of one or more clinically relevant lithium-target genes.
Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking at synapses.
Regulation of glutamate-mediated synaptic plasticity might play a role in the treatment of mood disorders, and raise new avenues for novel therapies for this devastating illness.
Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics.
Evidence from a variety of sources demonstrating regional reductions in central nervous system volume, as well as reductions in the numbers and/or sizes of glia and neurons in discrete brain areas suggests that mood disorders are associated with impairments of structural plasticity and cellular resilience.
The Role of the Extracellular Signal-Regulated Kinase Signaling Pathway in Mood Modulation
Lithium- and valproate-induced behavioral changes are qualitatively similar to the changes induced by amphetamine, a compound that induces relapse in remitted manic patients and mood elevation in normal subjects, suggesting that the ERK pathway may mediate the antimanic effects of mood stabilizers.
Neuroprotective effects of antidepressant and mood stabilizing drugs.
  • L. Young
  • Psychology, Biology
    Journal of psychiatry & neuroscience : JPN
  • 2002
Animal studies suggest that antidepressant and mood stabilizing drugs are neuroprotective and may also lead to neurogenesis in selected brain regions, and additional evidence obtained from the examination of brain tissue of patients with mood disorders supports the proposed targets of these drugs.
Antidepressants and neuroplasticity.
The results suggest that depression maybe associated with a disruption of mechanisms that govern cell survival and neural plasticity in the brain and antidepressants could mediate their effects by increasing neurogenesis and modulating the signaling pathways involved in plasticity and survival.
Long‐term action of lithium: A role for transcriptional and posttranscriptional factors regulated by protein kinase C
Evidence is presented to show that chronic lithium exerts significant transcriptional and posttranscriptional effects, and that these actions of lithium may be mediated via protein kinase C (PKC)‐induced alterations in nuclear transcription regulatory factors responsible for modulating the expression of proteins involved in long‐term neural plasticity and cellular response.
Glycogen Synthase Kinase-3β Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium
It is shown that lithium therapy activates Wnt signaling in vivo, as measured by increased Wnt-dependent gene expression in the amygdala, hippocampus, and hypothalamus, which supports a central role for GSK-3β in mediating behavioral responses to lithium.