title: Immunohistochemical evidence for impaired nitric oxide signaling of the locus coeruleus in bipolar disorder.
abstract: Nitric oxide (NO) is an important messenger in brain signaling and influences the balance of monoaminergic and glutamatergic neurotransmission. Alterations of NO signaling are thought to play a crucial role in the pathophysiology of mood disorders. The locus coeruleus (LC) comprises the largest group of norepinephrine containing neurons in the mammalian brain. These norepinephrinergic LC neurons are able to generate NO. Immunohistochemical staining of neuronal nitric oxide synthase (nNOS)-immunoreactive (ir) neurons was performed in the LC of the brains of 10 patients with bipolar I disorder (BD), 8 patients with major depressive disorder (MDD) and 16 control cases (C). Analysis of variance (ANOVA) revealed significant differences between the groups, and post hoc tests indicated a lower nNOS-ir neuron number in bipolar patients than in controls (left -34%, right -17%). The total number of Nissl-stained LC neurons showed no changes between major depressive disorder patients, bipolar patients and controls. In the mood disorder patients, illness duration correlated negatively with nNOS-ir neuronal number (r=-0.74, p=0.002). A reduced relative amount of NO in the LC of bipolar patients is likely a result of a compensation for increased glutamatergic activity. The current data on nNOS suggest a dysregulation of the nitrergic system in bipolar disorder. Future studies may clarify the potential role of glial cells in the context of the described nNOS deficit.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany. hbielau@freenet.de
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bielau
authors.forename: Ralf
authors.initials: R
authors.lastname: Brisch
authors.forename: Jenny
authors.initials: J
authors.lastname: Bernard-Mittelstaedt
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gos
authors.forename: Bruno
authors.initials: B
authors.lastname: Baumann
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000473:pathology*; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D052248:Nitric Oxide Synthase Type I