Astrocytic Hypertrophy in Anterior Cingulate White Matter of Depressed Suicides

Abstract

Increasing evidence suggests that cortical astrocytic function is disrupted in mood disorders and suicide. The fine neuroanatomy of astrocytes, however, remains to be investigated in these psychiatric conditions. In this study, we performed a detailed morphometric analysis of 3D-reconstructed gray and white matter astrocytes in Golgi-impregnated anterior cingulate cortex (ACC) samples from depressed suicides and matched controls. Postmortem ACC samples (BA24) from 10 well-characterized depressed suicides and 10 matched sudden-death controls were obtained from the Quebec Suicide Brain Bank. Golgi-impregnated protoplasmic astrocytes (gray matter, layer VI) and fibrous astrocytes (adjacent white matter) were reconstructed, and their morphometric features were analyzed using the Neurolucida software. For each cell, the soma size as well as the number, length, and branching of processes were determined. The densities of thorny protrusions found along the processes of both astrocytic subtypes were also determined. Protoplasmic astrocytes showed no significant difference between groups for any of the quantified parameters. However, fibrous astrocytes had significantly larger cell bodies, as well as longer, more ramified processes in depressed suicides, with values for these parameters being about twice as high as those measured in controls. These results provide the first evidence of altered cortical astrocytic morphology in mood disorders. The presence of hypertrophic astrocytes in BA24 white matter is consistent with reports suggesting white matter alterations in depression, and provides further support to the neuroinflammatory theory of depression.

Functional DNA methylation in a transcript specific 3′UTR region of TrkB associates with suicide

“…38 In addition, our group has found a hypertrophy of astrocytes, cells that act as modulator of the immune response in the CNS, 39 in the BA24 of suicide completers. 16 Finally, TrkB is part of an astrocytic gene network that has been reported as downregulated in the brain of suicide completers.…”

“…13 Downregulation of this truncated TrkB transcript, in coordination with a network of several other astrocytic genes, 14 has been reported in several brain regions of suicide completers. 9 Interestingly, convergent evidence from studies investigating gene expression patterns 15 to studies focusing on cell morphology, 16 has been increasingly suggesting that astrocyte dysregulation plays an important role in depression and suicide.…”

Astrocytic abnormalities and global DNA methylation patterns in depression and suicide

“…Astrocytes are multifaceted cells with numerous functions, including regulation of blood flow, synaptic communication and plasticity, immune regulation 7 and maintenance of neuronal functioning 8 . These -and other -physiological roles are likely impacted in depression and suicide given evidence from postmortem and animal studies showing altered astrocytic morphologies 5 and persistently decreased expression of astrocyte-specific genes, such as glial fibrillary acidic protein (GFAP) 9 , glutamine synthetase (GLUL) 10 , the glial high affinity transporters, SLC1A2 and SLC1A3 10 , aquaporin 4 (AQP4) 11 and the connexin genes Cx30 and Cx43 6 .…”

“…Glial cells account for at least 75% of brain cells 1 , and are implicated in a range of psychiatric disorders, including alcoholism 2 , schizophrenia 3 , depression 4 and suicide 5,6 . In particular, astrocytic dysfunction is evident in depressive psychopathologies, including suicide 4 .…”

L’apport de la recherche en psychologie dans la compréhension complexe de l’étiologie du suicide

“…Plus récemment, les études épigénétiques indiquent l'influence réciproque de ces méca-nismes (Labonté et al, 2012 ;McGowan et al, 2009 ;Turecki, 2012). La conjugaison de tous ces mécanismes aura une influence sur le dévelop-pement individuel en termes de type d'attachement, de pré sence ou d'absence de troubles de santé mentale, de capacités cognitives, de pensées, de réflexivité, de prises de décision et d'habiletés de coping, pour n'en nommer que quelques-uns (Beautrais et al, 2010 ;Kessler et al, 1997 ;Torres-Platas et al, 2011). Il faut aussi tenir compte du fait que ces mécanismes extrêmement complexes évolueront dans le temps (Labonté et Turecki, 2010).…”