Translating neurotrophic and cellular plasticity: from pathophysiology to improved therapeutics for bipolar disorder.
Summary of "Translating neurotrophic and cellular plasticity: from pathophysiology to improved therapeutics for bipolar disorder."
Soeiro-de-Souza MG, Dias VV, Figueira ML, Forlenza OV, Gattaz WF, Zarate Jr CA, Machado-Vieira R. Translating neurotrophic and cellular plasticity: from pathophysiology to improved therapeutics for bipolar disorder. Objective: Bipolar disorder (BD) likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. Therapeutic properties of mood stabilizers are presumed to result from a restoration of the function of these altered pathways and processes through a wide range of biochemical and molecular effects. We aimed to review the altered pathways and processes implicated in BD, such as neurotrophic factors, mitogen-activated protein kinases, Bcl-2, phosphoinositol signaling, intracellular calcium and glycogen synthase kinase-3. Methods: We undertook a literature search of recent relevant journal articles, book chapter and reviews on neurodegeneration and neuroprotection in BD. Search words entered were 'brain-derived neurotrophic factor,''Bcl-2,''mitogen-activated protein kinases,''neuroprotection,''calcium,''bipolar disorder,''mania,' and 'depression.' Results: The most consistent and replicated findings in the pathophysiology of BD may be classified as follows: i) calcium dysregulation, ii) mitochondrial/endoplasmic reticulum dysfunction, iii) glial and neuronal death/atrophy and iv) loss of neurotrophic/plasticity effects in brain areas critically involved in mood regulation. In addition, the evidence supports that treatment with mood stabilizers; in particular, lithium restores these pathophysiological changes. Conclusion: Bipolar disorder is associated with impairments in neurotrophic, cellular plasticity and resilience pathways as well as in neuroprotective processes. The evidence supports that treatment with mood stabilizers, in particular lithium, restores these pathophysiological changes. Studies that attempt to prevent (intervene before the onset of the molecular and cellular changes), treat (minimize severity of these deficits over time), and rectify (reverse molecular and cellular deficits) are promising therapeutic strategies for developing improved treatments for bipolar disorder.
Affiliation
Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of Sao Paulo (HC-FMUSP), São Paulo, Brazil Bipolar Disorder Research Program, Hospital Santa Maria, Faculty of Medicine, University of Lisbon, (FMUL), Lis
Journal Details
This article was published in the following journal.
Name: Acta psychiatrica Scandinavica
ISSN: 1600-0447
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22676371
- DOI: http://dx.doi.org/10.1111/j.1600-0447.2012.01889.x
Medical and Biotech [MESH] Definitions
Receptors, Nerve Growth Factor
Cell surface receptors that bind NERVE GROWTH FACTOR; (NGF) and a NGF-related family of neurotrophic factors that includes neurotrophins, BRAIN-DERIVED NEUROTROPHIC FACTOR and CILIARY NEUROTROPHIC FACTOR.
Ciliary Neurotrophic Factor Receptor Alpha Subunit
A ciliary neurotrophic factor receptor subunit. It is anchored to the cell surface via GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and has specificity for binding to CILIARY NEUROTROPHIC FACTOR. It lacks signal transducing domains which are found on the other two subunits of the receptor.
Ciliary Neurotrophic Factor
A neurotrophic factor that promotes the survival of various neuronal cell types and may play an important role in the injury response in the nervous system.
Neurotrophin 3
A neurotrophic factor involved in regulating the survival of visceral and proprioceptive sensory neurons. It is closely homologous to nerve growth factor beta and BRAIN-DERIVED NEUROTROPHIC FACTOR.
Receptor, Ciliary Neurotrophic Factor
Cell surface receptors for CILIARY NEUROTROPHIC FACTOR. They are heterotrimeric proteins formed by the association of the CILIARY NEUROTROPHIC FACTOR RECEPTOR ALPHA SUBUNIT with the LEUKEMIA INHIBITORY FACTOR RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130. Although the receptor regulates neuronal development, it is structurally similar to the cytokine receptor for INTERLEUKIN-6; (RECEPTORS, INTERLEUKIN-6).
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