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Neurosci Biobehav Rev. 2016 Jul;66:80-91. doi: 10.1016/j.neubiorev.2016.04.010. Epub 2016 Apr 22.

Targets of polyamine dysregulation in major depression and suicide: Activity-dependent feedback, excitability, and neurotransmission.

Author information

1
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA.
2
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA. Electronic address: psequeir@uci.edu.

Abstract

Major depressive disorder (MDD) is a leading cause of disability worldwide characterized by altered neuronal activity in brain regions involved in the control of stress and emotion. Although multiple lines of evidence suggest that altered stress-coping mechanisms underlie the etiology of MDD, the homeostatic control of neuronal excitability in MDD at the molecular level is not well established. In this review, we examine past and current evidence implicating dysregulation of the polyamine system as a central factor in the homeostatic response to stress and the etiology of MDD. We discuss the cellular effects of abnormal metabolism of polyamines in the context of their role in sensing and modulation of neuronal, electrical, and synaptic activity. Finally, we discuss evidence supporting an allostatic model of depression based on a chronic elevation in polyamine levels resulting in self-sustained stress response mechanisms maintained by maladaptive homeostatic mechanisms.

KEYWORDS:

Excitability; Homeostasis; Ion channels; Major depression; Neurotransmitter receptors; Polyamine system; Suicide

PMID:
27108532
PMCID:
PMC5096383
DOI:
10.1016/j.neubiorev.2016.04.010
[Indexed for MEDLINE]
Free PMC Article

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