Stereological investigation of the posterior hippocampus in affective disorders

Abstract

Hippocampus volumes have been shown to be decreased in patients with major depression, but volume measurements are inconsistent in patients with bipolar disorder. Both disorders are associated with deficits in hippocampus-mediated cognitive functions. However, the underlying pathophysiology is widely unknown. In this post-mortem study, we used design-based stereology on Nissl-stained serial sections to investigate the number of neurons, oligodendrocytes and astrocytes in substructures of the posterior hippocampus in eight patients with major depression, eight patients with bipolar disorder and ten control patients without a neuropsychiatric disorder. Compared to controls, patients with bipolar disorder had significantly more neurons in the cornu ammonis subfield 1 (CA1) and the subiculum, while the number of oligodendrocytes was higher only in CA1. In patients with major depression, the density of oligodendrocytes was higher in CA2/3, CA4 and the subiculum. The dose of antidepressants correlated with the density and number of oligodendrocytes in CA2/3, indicating that antidepressants may affect our results. Treatment with neuroleptics expressed in chlorpromazine equivalents and benzodiazepines expressed in diazepam equivalents correlated negatively with the number of oligodendrocytes in CA2/3 and CA4, respectively, suggesting that treatment with these drugs do not influence cell number. We did not detect alterations in either volumes of substructures or numbers of astrocytes. Increased cell numbers argue for a denser packing of neurons and oligodendrocytes as a result of a decreased neuropils. This neuropathological process may be based on neurodevelopmental disturbances and may contribute to altered microconnectivity and cognitive deficits in affective disorders.

Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder

“…There were no significant changes in either astrocyte number or density in CA4 (“hilus” in the present study) in MDD as compared to control subjects. The lack of a significant change in astrocyte number or density in the presence of antidepressant medications at the time of death in both Gos et al (2013) and Malchow et al (2015) is consistent with the present study where there was no significant difference in the density of GFAP-ir astrocytes between antidepressant-treated subjects with MDD and control subjects.…”

“…It remains to be determined if the S100B antibody labels a population of astrocytes not labeled by the GFAP antibody or if it labels a subpopulation of astrocytes that are also labeled by the GFAP antibody. Recently, using mostly the same depressed subjects as in Gos et al (2013), Malchow et al (2015), using Nissl plus myelin staining, examined the cell number and density of the total population of astrocytes in the left and right posterior hippocampus. There were no significant changes in either astrocyte number or density in CA4 (“hilus” in the present study) in MDD as compared to control subjects.…”

Neuron-glia Interaction as a Possible Pathophysiological Mechanism of Bipolar Disorder

“…Neuropathological findings have shown some glial alterations in bipolar disorder [ 12 , 19 , 20 - 22 ]. A histological study of the subgenual portion of Brodmann area 24 showed a reduced number of glial cells in the brains of patients with bipolar disorder, especially in those with a family history of mood disorder [ 23 ].…”

“…At last, it is worth mentioning that a morphometric study showed reduction in the numerical density of oligodendroglial cells in layer VI and Broadmann area 9 in the brains of patients with bipolar disorder [ 19 ]. Another postmortem study showed a higher number of oligodendrocytes in the hippocampal CA1 area of patients with bipolar disorder [ 20 ]. Some neuropathological findings of glia in bipolar disorder are summarized in the Table 1 .…”

Reduced density of glutamine synthetase immunoreactive astrocytes in different cortical areas in major depression but not in bipolar I disorder

“…However, during the last years a wave of information appeared to suggest that glial cells prominently, and in many ways, contribute to brain structural and functional changes in mood disorders. In numerous histological postmortem investigations both significantly reduced ( Öngür et al, 1998 ; Rajkowska, 2000 ; Cotter et al, 2001a , b ; Hamidi et al, 2004 ; Uranova et al, 2004 ; Rajkowska and Miguel-Hidalgo, 2007 ; Altshuler et al, 2010 ; Gos et al, 2013 ) and increased ( Davis et al, 2002 ; Mosebach et al, 2013 ; Malchow et al, 2014 ) glial cell numbers and numerical densities have been observed in prefrontal cortex areas and limbic regions. In addition, characteristic changes in gene expression patterns and metabolic pathways of glial cells have been found in affective disorders (reviewed in Barley et al, 2009 ; Steiner et al, 2012 ; Mosebach et al, 2013 ; Duncan et al, 2014 ; Schroeter et al, 2014 ; Bernstein et al, 2015 ).…”