Post-mortem-Untersuchungen zu neuronalen Aktivierungsmustern bei depressiven Patienten

T. Gos; B. Bogerts; J. Steiner

doi:10.1055/s-0038-1628445

Nervenheilkunde, Table of Contents

Nervenheilkunde 2011; 30(11): 909-913
DOI: 10.1055/s-0038-1628445

Depression

Schattauer GmbH

Post-mortem-Untersuchungen zu neuronalen Aktivierungsmustern bei depressiven Patienten

Welchen Einfluss haben Suizidalität und Unipolar-bipolar-Dichotomie?Neuronal activity patterns in depression assessed post mortemWhich impacts have suicidality and unipolar-bipolar dichotomy?

T. Gos

¹Institut für Rechtsmedizin, Medizinische Universität Danzig, Polen

²Klinik für Psychiatrie und Psychotherapie, Universität Magdeburg

³Institut für Biologie, Abteilung Zoologie/Entwicklungsneurobiologie, Universität Magdeburg

,

B. Bogerts

²Klinik für Psychiatrie und Psychotherapie, Universität Magdeburg

,

J. Steiner

²Klinik für Psychiatrie und Psychotherapie, Universität Magdeburg

⁴Pembroke College, Universität Cambridge, Großbritannien

› Author Affiliations

Abstract

Zusammenfassung

In unserem Übersichtsartikel fassen wir Ergebnisse von Post-mortem-Studien an Material der Magdeburger Hirnbank zusammen, deren Schwerpunkt eine Evaluation neuronaler Aktivierungsmuster in depressionsrelevanten Netzwerken war. Chronische Veränderungen der Aktivität ribosomaler DNA in Nervenzellen wurden durch den quantitativen Nachweis von argyrophilen mit Nukleolus Organisator Regionen assoziierten Proteinen (AgNOR) in präfrontal-limbischen Hirnregionen, im Mandelkern, striato-pallidalen Komplex und serotonergen dorsalen Raphekern untersucht. Der Einfluss des Faktors Suizidalität war stärker als der Unterschied zwischen unipolarer und bipolarer Depression. Unsere Ergebnisse unterstützen die Sichtweise, dass Suizidalität und Depression eine teils eigenständige neurobiologische Grundlage aufweisen. Neue Therapiestrategien sind erforderlich, um die suizidspezifische Hirnpathologie effektiv zu beeinflussen.

Summary

In our review we present postmortem results from the Magdeburg Brain Bank related to the evaluation of impaired activity of neuronal networks relevant for depression. Chronic changes in ribosomal DNA activity in neurons of prefrontal limbic regions, the amygdala, the striato-pallidal complex, and the serotonergic dorsal raphe nucleus have been revealed by quantitative evaluation of silver-stained nucleolar organising regions (AgNORs). The impact of processes leading to suicide has been accentuated in opposite to the weak influence of unipolar-bipolar dichotomy. Our results support the view that suicide and depression are phenomena of overlapping but distinct neurobiology. They suggest also that new specific therapeutic strategies are needed to prevent more effectively brain abnormalities related to suicide.

Schlüsselwörter

Depression - bipolare Störung - post mortem - AgNOR-Färbung

Keywords

Major depression - bipolar disorder - post mortem - AgNOR staining

Full Text

References

Literatur
1 Alt SR. et al. Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 2010; 35 (04) 544-56.
2 Arango V. et al. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001; 25 (06) 892-903.
3 Austin MC, Janosky JE, Murphy HA. Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. Mol Psychiatry 2003; 08 (03) 324-32.
4 Bach-Mizrachi H. et al. Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Neuropsychopharmacology 2006; 31 (04) 814-24.
5 Barbas H. Specialized elements of orbitofrontal cortex in primates. Ann N Y Acad Sci 2007; 1121: 10-32.
6 Bielau H. et al. Differences in activation of the dorsal raphe nucleus depending on performance of suicide. Brain Res 2005; 1039 (1–2): 43-52.
7 Boldrini M, Underwood MD, Mann JJ, Arango V. Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides. J Psychiatr Res 2008; 42 (06) 433-42.
8 Bonelli RM, Kapfhammer HP, Pillay SS, Yurgelun-Todd DA. Basal ganglia volumetric studies in affective disorder: what did we learn in the last 15 years?. J Neural Transm 2006; 113 (02) 255-68.
9 Bonkale WL, Turecki G, Austin MC. Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressed suicide subjects is restricted to the dorsal subnucleus. Synapse 2006; 60 (01) 81-5.
10 Burgdorf J, Panksepp J. The neurobiology of positive emotions. Neurosci Biobehav Rev 2006; 30 (02) 173-87.
11 Buzsaki G, Kaila K, Raichle M. Inhibition and brain work. Neuron 2007; 56 (05) 771-83.
12 Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000; 04 (06) 215-22.
13 Cerullo MA, Adler CM, Delbello MP, Strakowski SM. The functional neuroanatomy of bipolar disorder. Int Rev Psychiatry 2009; 21 (04) 314-22.
14 Derenzini M. The AgNORs. Micron 2000; 31 (02) 117-20.
15 Ding Q, Markesbery WR, Chen Q, Li F, Keller JN. Ribosome dysfunction is an early event in Alzheimer’s disease. J Neurosci 2005; 25 (40) 9171-5.
16 Emsell L, McDonald C. The structural neuroimaging of bipolar disorder. Int Rev Psychiatry 2009; 21 (04) 297-313.
17 Fountoulakis KN, Giannakopoulos P, Kovari E, Bouras C. Assessing the role of cingulate cortex in bipolar disorder: neuropathological, structural and functional imaging data. Brain Res Rev 2008; 59 (01) 9-21.
18 Freedman LJ, Insel TR, Smith Y. Subcortical projections of area 25 (subgenual cortex) of the macaque monkey. J Comp Neurol 2000; 421 (02) 172-88.
19 Galvan A, Wichmann T. Pathophysiology of parkinsonism. Clin Neurophysiol 2008; 119 (07) 1459-74.
20 Garcia LMMoreno, Cimadevilla JM, Gonzalez HPardo, Zahonero MC, Arias JL. NOR activity in hippocampal areas during the postnatal development and ageing. Mech Ageing Dev 1997; 97 (02) 173-81.
21 Gos T. et al. The changes of AgNOR parameters of anterior cingulate pyramidal neurons are regionspecific in suicidal and non-suicidal depressive patients. World J Biol Psychiatry 2007; 08 (04) 245-55.
22 Gos T. et al. Demonstration of decreased activity of dorsal raphe nucleus neurons in depressed suicidal patients by the AgNOR staining method. J Affect Disord 2008; 111 (2–3): 251-60.
23 Gos T. et al. Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients. Eur Arch Psychiatry Clin Neurosci 2008; 258 (08) 513-20.
24 Gos T. et al. Demonstration of disturbed activity of orbitofrontal pyramidal neurons in depressed patients by the AgNOR staining method. J Affect Disord 2009; 118 (1–3): 131-8.
25 Gos T. et al. Demonstration of disturbed activity of external globus pallidus projecting neurons in depressed patients by the AgNOR staining method. J Affect Disord 2009; 119 (1–3): 149-55.
26 Gos T. et al. Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-Immunoreactive neuropil. J Affect Disord 2009; 113 (1–2): 45-55.
27 Gos T. et al. Demonstration of disturbed activity of the lateral amygdaloid nucleus projection neurons in depressed patients by the AgNOR staining method. J Affect Disord 2010; 126 (03) 402-10.
28 Grangeon MC. et al. White matter hyperintensities and their association with suicidality in major affective disorders: a meta-analysis of magnetic resonance imaging studies. CNS Spectr 2010; 15 (06) 375-81.
29 Graybiel AM. Habits, rituals, and the evaluative brain. Annu Rev Neurosci 2008; 31: 359-87.
30 Graybiel AM. The basal ganglia: learning new tricks and loving it. Curr Opin Neurobiol 2005; 15 (06) 638-44.
31 Haber SN. The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 2003; 26 (04) 317-30.
32 Hajek T, Kozeny J, Kopecek M, Alda M, Hoschl C. Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. J Psychiatry Neurosci 2008; 33 (02) 91-9.
33 Harrison PJ. The neuropathology of primary mood disorder. Brain 2002; 125 (07) 1428-49.
34 Hayashida M. et al. Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33 (04) 581-8.
35 Hercher C, Turecki G, Mechawar N. Through the looking glass: examining neuroanatomical evidence for cellular alterations in major depression. J Psychiatr Res 2009; 43 (11) 947-61.
36 Holland PC, Gallagher M. Amygdala-frontal interactions and reward expectancy. Curr Opin Neurobiol 2004; 14 (02) 148-55.
37 Janczukowicz J. The prognostic role of proliferation activity in human CNS tumours: the determination of AgNOR, PCNA and Ki-67 expression. Part 1: AgNOR expression in CNS tumours. Folia Neuropathol 2003; 41 (02) 97-101.
38 Johnson LR. et al. A recurrent network in the lateral amygdala: a mechanism for coincidence detection. Front Neural Circuits 2008; 02: 3.
39 Jordan BA, Fernholz BD, Khatri L, Ziff EB. Activitydependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons. Nat Neurosci 2007; 10 (04) 427-35.
40 Klempan TA, Ernst C, Deleva V, Labonte B, Turecki G. Characterization of QKI gene expression, genetics, and epigenetics in suicide victims with major depressive disorder. Biol Psychiatry 2009; 66 (09) 824-31.
41 Krishnan V, Nestler EJ. Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 2010; 167 (11) 1305-20.
42 Levesque M, Parent A. The striatofugal fiber system in primates: a reevaluation of its organization based on single-axon tracing studies. Proc Natl Acad Sci USA 2005; 102 (33) 11888-93.
43 Lloyd KG, Farley IJ, Deck JH, Hornykiewicz O. Serotonin and 5-hydroxyindoleacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharmacol 1974; 11 (00) 387-97.
44 Logothetis NK. What we can do and what we cannot do with fMRI. Nature 2008; 453 (7197): 869-78.
45 Mann JJ. Neurobiology of suicidal behaviour. Nat Rev Neurosci 2003; 04 (10) 819-28.
46 Mann JJ, Currier DM. Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression. Eur Psychiatry 2010; 25 (05) 268-71.
47 McGowan PO, Szyf M. The epigenetics of social adversity in early life. Neurobiol Dis 2010; 39 (01) 66-72.
48 McNab F, Klingberg T. Prefrontal cortex and basal ganglia control access to working memory. Nat Neurosci 2008; 11 (01) 103-7.
49 Mennel HD, Müller I. Morphometric investigation on nuclear and nucleolar arrangement and AgNOR content in the rat hippocampus under normal and ischemic conditions. Exp Toxicol Pathol 1994; 46 (06) 491-501.
50 Mitchell ND, Baker GB. An update on the role of glutamate in the pathophysiology of depression. Acta Psychiatr Scand 2010; 122 (03) 192-210.
51 Murray EA. The amygdala, reward and emotion. Trends Cogn Sci 2007; 01 (11) 489-97.
52 Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34 (01) 13-25.
53 Northoff G. et al. Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study. Cereb Cortex 2000; 10 (01) 93-107.
54 Öngür D, Price JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 2000; 10 (03) 206-19.
55 Parent A, Hazrati LN. Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 1995; 20 (01) 128-54.
56 Person AL, Perkel DJ. Pallidal neuron activity increases during sensory relay through thalamus in a songbird circuit essential for learning. J Neurosci 2007; 27 (32) 8687-98.
57 Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 2010; 36 (01) 183-206.
58 Ploton D. Structure and molecular organization of the nucleolus. Zentralbl Pathol 1994; 140 (01) 3-6.
59 Poulter MO. et al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry 2008; 64 (08) 645-52.
60 Price JL. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann N Y Acad Sci 2007; 1121: 54-71.
61 Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology 2010; 35 (01) 192-216.
62 Purselle DC, Nemeroff CB. Serotonin transporter: a potential substrate in the biology of suicide. Neuropsychopharmacology 2003; 28 (04) 613-9.
63 Quinones-Hinojosa A, Sanai N, Smith JS, McDermott MW. Techniques to assess the proliferative potential of brain tumors. J Neurooncol 2005; 74 (01) 19-30.
64 Raichle ME. Two views of brain function. Trends Cogn Sci 2010; 14 (04) 180-90.
65 Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 2007; 06 (03) 219-33.
66 Raska I, Shaw PJ, Cmarko D. New insights into nucleolar architecture and activity. Int Rev Cytol 2006; 255: 177-235.
67 Rolls ET. et al. Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices. Cereb Cortex 2003; 13 (03) 308-17.
68 Rüschoff J, Elsasser HP, Adler G. Correlation of nucleolar organizer regions with secretory and regenerative process in experimental cerulein-induced pancreatitis in the rat. Pancreas 1995; 11 (02) 154-9.
69 Savitz J, Lucki I, Drevets WC. 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol 2009; 88 (01) 17-31.
70 Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 2009; 33 (05) 699-771.
71 Scharinger C, Rabl U, Sitte HH, Pezawas L. Imaging genetics of mood disorders. Neuroimage 2010; 53 (03) 810-21.
72 Schiff ND. Central thalamic contributions to arousal regulation and neurological disorders of consciousness. Ann N Y Acad Sci 2008; 1129: 105-18.
73 Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci 2004; 07 (08) 489-95.
74 Sibille E. et al. A molecular signature of depression in the amygdala. Am J Psychiatry 2009; 166 (09) 1011-24.
75 Siever LJ. Neurobiology of aggression and violence. Am J Psychiatry 2008; 165 (04) 429-42.
76 Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D. Nucleolus: the fascinating nuclear body. Histochem Cell Biol 2008; 129 (01) 13-31.
77 Smith Y, Raju DV, Pare JF, Sidibe M. The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci 2004; 27 (09) 520-7.
78 Sokoloff L. The physiological and biochemical bases of functional brain imaging. Cogn Neurodyn 2008; 02 (01) 1-5.
79 Steiner J. et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res 2008; 42 (02) 151-7.
80 Stockmeier CA. Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 2003; 37 (05) 357-73.
81 Underwood MD. et al. Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. Biol Psychiatry 1999; 46 (04) 473-83.
82 Wagner G, Koch K, Schachtzabel C, Schultz CC, Sauer H, Schlosser RG. Structural brain alterations in patients with major depressive disorder and high risk for suicide: evidence for a distinct neurobiological entity?. Neuroimage 2011; 54 (02) 1607-14.
83 Wittmann M. et al. Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling. J Neurosci 2009; 29 (47) 14687-700.
84 Young LT, Bezchlibnyk YB, Chen B, Wang JF, Mac-Queen GM. Amygdala cyclic adenosine monophosphate response element binding protein phosphorylation in patients with mood disorders: effects of diagnosis, suicide, and drug treatment. Biol Psychiatry 2004; 55 (06) 570-7.