Hippocampal Angiogenesis and Progenitor Cell Proliferation Are Increased with Antidepressant Use in Major Depression

被引：256

作者：

Boldrini, Maura ^{[1
,5
,7
]}

Hen, Rene ^{[1
,2
,3
,6
]}

Underwood, Mark D. ^{[1
,5
]}

Rosoklija, Gorazd B. ^{[1
,5
,8
]}

Dwork, Andrew J. ^{[1
,4
,5
]}

Mann, J. John ^{[1
,5
]}

Arango, Victoria ^{[1
,5
]}

机构：

[1] Columbia Univ, Dept Psychiat, New York, NY 10032 USA

[2] Columbia Univ, Dept Neurosci, New York, NY 10032 USA

[3] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA

[4] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[5] New York State Psychiat Inst & Hosp, Div Mol Imaging & Neuropathol, New York, NY 10032 USA

[6] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA

[7] Univ Florence, Dept Neurol & Psychiat Sci, Florence, Italy

[8] Macedonian Acad Sci & Arts, Skopje, North Macedonia

来源：

BIOLOGICAL PSYCHIATRY | 2012年 / 72卷 / 07期

关键词：

Dentate gyrus; immunohistochemistry; nestin; neural progenitor cells; postmortem; stereology; 5-HT2A SEROTONINERGIC RECEPTOR; NEUROGENESIS IN-VITRO; NITRIC-OXIDE SYNTHASE; DENTATE GYRUS; NESTIN EXPRESSION; STEM-CELL; IMMUNOHISTOCHEMICAL EXPRESSION; POSTMORTEM INTERVAL; BEHAVIORAL ACTIONS; ENDOTHELIAL-CELL;

D O I：

10.1016/j.biopsych.2012.04.024

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Adult neurogenesis is coupled to angiogenesis in neurogenic niches in the dentate gyrus (DG) and increased by antidepressants in rodents. We hypothesized that, in major depressive disorder (MDD), antidepressants increase neural progenitor cells (NPCs) and capillaries in the human DG. Methods: Neural progenitor cells and capillaries, detected on hippocampal sections by immunohistochemistry for neural stem cell protein, were quantified by stereology in matched MDDs (untreated, n = 12), MDD treated with selective serotonin reuptake inhibitors (MDD*SSRI, n = 6) or tricyclic antidepressants (MDD*TCA, n = 6), and nonpsychiatric control subjects (n = 12), all confirmed by psychological autopsy. Results: The MDD*SSRI had a larger capillary area and more NPCs versus MDDs (p = .034 and p = .008, respectively) and control subjects (p = .010 and p = .002, respectively) in the whole DG, more NPCs in the anterior (pes, p = .042) and central (midbody, p = .004) DG, and greater capillary area in the pes (p = .002) and midbody (p = .021). The NPC number and capillary area correlated positively in the whole sample (R-2 = .454, p < .001) and in treated subjects (R-2 = .749, p = .001). We found no NPCs or antidepressant-related angiogenesis in CA1 and parahippocampal gyrus. The DG volume correlated positively with NPC number (p = .004) and capillary area (p < .001) and differed between groups in whole hippocampus (p = .013) and midbody (p = .036). Age negatively correlated with NPC number (p = .042), capillary area (p = .037), and bifurcations (p = .030). No gender effect was detected. Conclusions: Antidepressants increase human hippocampal NPCs and angiogenesis selectively in the anterior and mid DG. These results raise the possibility of a causal relationship between angiogenesis and neurogenesis, as seen in other proliferating tissues, and support their possible role in the mechanism of action of antidepressants.

引用

页码：562 / 571

页数：10

共 102 条

[31] Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo [J].