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.

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It is unclear what the decrease in medial prefrontal cortex grey matter volume represents in chronic pain. The most attractive reason is neurodegeneration. However, there is no evidence to support this. Our review reveals nondegenerative causes of decreased medial prefrontal grey matter to guide future research into chronic pain pathophysiology.

ObjectiveTo determine whether virally suppressed HIV neuropathogenesis, a chronic neuroinflammatory state, promotes abnormal brain amyloid deposition.MethodsA total of 10 men with virally suppressed HIV-associated neurocognitive disorder (HAND), aged 46–68 years, underwent 11C-labeled Pittsburgh compound B PET. Data from the Australian Imaging, Biomarkers and Lifestyle (AIBL), including 39 cognitively normal individuals (aged 60–74 years), 7 individuals with mild cognitive impairment (MCI) (aged 64–71 years), and 11 individuals with Alzheimer disease (AD) (aged 55–74 years), were used as reference. Apart from more women, the AIBL cohort was demographically comparable with the HIV sample. Also, the AIBL PET data did not differ by sex. Cerebellum standardized uptake value ratio amyloid values within 22 regions of interest were estimated. In the HIV sample, apolipoprotein E (APOE) was available in 80%, CSF biomarkers in 60%, and 8–10 years of long-term health outcomes in 100%.ResultsHAND and the AIBL group with no cognitive deficits had similar amyloid deposition, which was lower than that in both the MCI and AD groups. At the individual level, one HAND case showed high amyloid deposition consistent with AD. This case also had a CSF-AD–like profile and an E4/E4 for APOE. Clinically, this case declined over 18 years with mild HAND symptoms first, followed by progressive memory decline 8–9 years after the study PET, then progression to severe dementia within 2–3 years, and lived a further 6 years. Another HAND case showed increased amyloid deposition restricted to the hippocampi. Two other HAND cases showed abnormally decreased amyloid in subcortical areas.ConclusionsRelative to cognitively normal older controls, brain amyloid burden does not differ in virally suppressed HAND at the group level. However, individual analyses show that abnormally high and low amyloid burden occur.

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence.