HIPPOCAMPAL ANGIOGENESIS AND PROGENITOR CELL PROLIFERATION ARE INCREASED WITH ANTIDEPRESSANT USE IN MAJOR DEPRESSION

By M. Boldrini, R. Hen, M. Underwood, G. Rosoklija, A. Dwork, J. Mann, V. Arango. 2012

336 citations recorded by the source corpus.

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 NPCs and capillaries, detected on hippocampal sections by immunohistochemistry for nestin, 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 controls (n=12), all confirmed by psychological autopsy. Results MDD*SSRI had a larger capillary area and more NPCs versus MDDs (p=.034 and p=.008, respectively) and controls (p=.010 and p=.002, respectively) in the whole DG, more NPCs in the anterior (pes, p=.042) and central (mid-body, p=.004) DG, and greater capillary area in the pes (p=.002) and mid-body (p=.021). NPC number and capillary area correlated positively in the whole sample (R2=.454, p<.001) and in treated subjects (R2=.749, p=.001). We found no NPCs or antidepressant-related angiogenesis in CA1 and parahippocampal gyrus. DG volume correlated positively with NPC number (p=.004) and capillary area (p<.001), and differed between groups in whole hippocampus (p=.013) and mid-body (p=.036). Age negatively correlated with NPC number (p=.042), capillary area (p=.037) and bifurcations (p=.030). No sex 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.

Subfields: Behavioral Neuroscience, Cellular and Molecular Neuroscience, Developmental Neuroscience

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Behavioral Neuroscience

1. A. Feder
2. R. Hen
3. Melody V. Wu
4. Dennis S. Charney
5. A. Masten
6. E. Nestler
7. D. Cicchetti
8. V. Krishnan

In Cellular and Molecular Neuroscience

1. R. Hen
2. Robin L. Carhart-Harris
3. A. Dwork
4. G. Rosoklija
5. V. Arango
6. M. Boldrini
7. David J. Nutt
8. Melody V. Wu

In Developmental Neuroscience

1. R. Hen
2. V. Arango
3. A. Dwork
4. G. Rosoklija
5. M. Boldrini
6. Melody V. Wu
7. A. Feder
8. Dennis S. Charney

Citations in the corpus

• Human Hippocampal Neurogenesis Persists throughout Aging (2018, positive): “Nestin is a marker of newly formed blood vessels (Boldrini et al., 2012; Salehi et al., 2008) and co-labels with collagen-IV, a vascular basement membrane marker, and platelet/ endothelial cell adhesion molecule (PECAM, or CD31), a marker of endothelial cells (Boldrini et al., 2012).”
• Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders (2014, neutral): “Immunohistochemistry and stereology were performed as previously described (Boldrini et al., 2009, 2012, 2013).”
• Understanding resilience (2013, background): “As the hippocampus is one of the most plastic regions of the brain, there is hope that pharmacological treatments, such as antidepressants, may be able to reverse this decrease in volume by increasing neural progenitor cells (Boldrini et al., 2012).”
• Serotonin and brain function: a tale of two receptors (2017, result): “Chronic treatment with SSRIs has been associated with increased neurogenesis (Boldrini et al., 2009), particularly in the hippocampus (Boldrini et al., 2009, 2012) and some improvements in learning and cognition (Bui et al., 2013), albeit with some contradictory findings (Deakin et al., 2004).”
• Functional Dissociation of Adult-Born Neurons Along the Dorsoventral Axis of the Dentate Gyrus (2014, background): “…administration has also been shown to result in increased numbers of neural progenitors and mature granule cells specifically in the rostral (homologous to the ventral in rodents) dentate gyrus granule cell layer of depressed patients compared to untreated controls (Boldrini et al., 2012, 2013).”