Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders

Neuropharmacology. 2012 Jan;62(1):237-46. doi: 10.1016/j.neuropharm.2011.07.012. Epub 2011 Jul 22.


The diamine agmatine may serve as a precursor in polyamine synthesis. In addition, agmatine may also act as a neurotransmitter, binding to imidazoline receptors. Behaviorally, agmatine exerts antidepressant-like effects. The enzyme agmatinase degrades agmatine. The gene coding for human agmatinase is located on chromosome 1p36, a gene locus which has been linked to bipolar disorder and major depression, but the enzyme has not yet been studied in the context of neuropsychiatric diseases. We analyzed agmatinase protein expression in postmortem hippocampi of individuals with affective disorders. Data from eleven patients with mood disorders (unipolar and bipolar depression) and twelve matched control cases were compared by immunocytochemical and morphometrical analysis. Agmatinase protein was detected in a subset of hippocampal interneurons. The protein was localized to perikarya, neurites and putative nerve endings contacting hippocampal pyramidal neurons and dentate gyrus granule cells. The number and the numerical density of agmatinase-immunopositive cell bodies were strongly elevated in depressive patients. In addition, a significantly increased density of agmatinase-immunoreactive punctate profiles was observed in the CA(4) region in unipolar and bipolar depression. The reported increased expression of agmatinase suggests a functional relevance of the enzyme in the pathophysiology of human affective disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Cationic Amino Acid Transporter 1 / metabolism
  • Cationic Amino Acid Transporter 2 / metabolism
  • Cell Count
  • Female
  • Hippocampus / pathology*
  • Humans
  • Interneurons / drug effects
  • Interneurons / enzymology*
  • Male
  • Middle Aged
  • Mood Disorders / drug therapy
  • Mood Disorders / pathology*
  • Parvalbumins / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*
  • Ureohydrolases / metabolism*


  • Antidepressive Agents
  • Cationic Amino Acid Transporter 1
  • Cationic Amino Acid Transporter 2
  • Parvalbumins
  • Ureohydrolases
  • agmatinase