Stress-Induced Grey Matter Loss Determined by MRI Is Primarily Due to Loss of Dendrites and Their Synapses

Abstract

Stress, unaccompanied by signs of post-traumatic stress disorder, is known to decrease grey matter volume (GMV) in the anterior cingulate cortex (ACC) and hippocampus but not the amygdala in humans. We sought to determine if this was the case in stressed mice using high-resolution magnetic resonance imaging (MRI) and to identify the cellular constituents of the grey matter that quantitatively give rise to such changes. Stressed mice showed grey matter losses of 10 and 15 % in the ACC and hippocampus, respectively but not in the amygdala or the retrosplenial granular area (RSG). Concurrently, no changes in the number or volumes of the somas of neurons, astrocytes or oligodendrocytes were detected. A loss of synaptic spine density of up to 60 % occurred on different-order dendrites in the ACC and hippocampus (CA1) but not in the amygdala or RSG. The loss of spines was accompanied by decreases in cumulative dendritic length of neurons of over 40 % in the ACC and hippocampus (CA1) giving rise to decreases in volume of dendrites of 2.6 mm(3) for the former and 0.6 mm(3) for the latter, with no change in the amygdala or RSG. These values are similar to the MRI-determined loss of GMV following stress of 3.0 and 0.8 mm(3) in ACC and hippocampus, respectively, with no changes in the amygdala or RSG. This quantitative study is the first to relate GMV changes in the cortex measured with MRI to volume changes in cellular constituents of the grey matter.

Lower anterior cingulate volume in seriously violent men with antisocial personality disorder or schizophrenia and a history of childhood abuse

“…The AC is highly vulnerable to stress-related changes in noradrenergic activity (Hermans et al, 2011) and, like the hippocampus, shows grey matter loss following a variety of stressful conditions, including childhood adversity, in individuals with or without a PTSD diagnosis (Ansell et al, 2012;Dannlowski et al, 2012;Karl et al, 2006). Although the current study is unable to conclusively inform about the direction of causality in the observed relationship between AC volume and psychosocial deprivation/abuse, a number of studies have clearly shown AC grey matter loss in people experiencing stressful life events and cumulative life adversities with no psychiatric diagnosis (Ansell et al, 2012;Ganzel et al, 2008;Papagni et al, 2011), as well as in animals following exposure to stress (Cerqueira et al, 2005;Kassem et al, 2013).…”

Spine synapse remodeling in the pathophysiology and treatment of depression

“…Stress exposure has been shown to result in spine loss in hippocampus CA3 cells [69, 89, 92, 98, 106, 107], although increased or no change in spine density has also been reported [72, 108]. Stress-induced spine loss has been shown in CA1 (and CA3) along with impaired synaptic transmission and depressive behaviors [49, 92]. Decreased spine densities in CA1 neurons has been associated with depression-like behaviors in a light-induced depression model, in the absence of spine changes in CA3 or dendritic changes in CA3 or CA1 [4].…”

Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder

“…It has been suggested that abnormal regional brain volume in OCD might result from a combination of abnormal neurodevelopmental processes and additional altered aging-related trajectories due to several factors operating on multiple levels-for example, genetic variations influencing neuronal pruning and aging processes, activity-dependent neuronal plasticity associated with chronic symptoms or compensatory processes, and neurochemical effects of pharmacological treatment or stress (30,31). Patients showed relative preservation of the putamen, nucleus accumbens, and inferior and orbitofrontal cortex during aging, which was in contrast to the loss associated with healthy aging (18).…”

“…The fusiform, parahippocampal, and inferior temporal cortices are involved in higher-level visual processing, visual emotional perception (39), and emotional memory formation (40). Greater volume loss in these regions may thus be related to chronic stress and the exaggerated emotional responsiveness seen in OCD (1,31).…”