A neurotrophic model for stress-related mood disorders.

Mood disorders and allostatic load.

OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from de...

http://sites.oxy.edu/clint/physio/article/theroleofinsufficientglucocorticoidsignalinginstressrelateddisorders.pdf

When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders

The stress system in the human brain in depression and neurodegeneration.

Converging lines of research suggest that the hippocampal complex (HC) may have a role in the pathophysiology of major depressive disorder (MDD). Although postmortem studies show little cellular death in the HC of depressed patients, animal studies suggest that elevated glucocorticoid levels associated with MDD may negatively affect neurogenesis, cause excitotoxic damage or be associated with reduced levels of key neurotrophins in the HC. Antidepressant medications may counter these effects, having been shown to increase HC neurogenesis and levels of brain-derived neurotrophic factor in animal studies. Neuropsychological studies have identified deficits in hippocampus-dependent recollection memory that may not abate with euthymia, and such memory impairment has been the most reliably documented cognitive abnormality in patients with MDD. Finally, data from imaging studies suggest both structural changes in the volume of the HC and functional alterations in frontotemporal and limbic circuits that may be critical for mood regulation. The extent to which such functional and structural changes determine clinical outcome in MDD remains unknown; a related, but also currently unanswered, question is whether the changes in HC function and structure observed in MDD are preventable or modifiable with effective treatment for the depressive illness.

/pdf/the-role-of-the-hippocampus-in-the-pathophysiology-of-major-2sqbvc0cxu.pdf

The role of the hippocampus in the pathophysiology of major depression.

Glucocorticoid (GC) overexposure in animals has been implicated in hippocampal dysfunctioning and neuronal loss. In major depression, hypercortisolemia, hypothalamic-pituitary-adrenocortical-axis alterations, and reduced hippocampal volumes are commonly observed; hence, hippocampal neurodegeneration is also expected. To study possible GC-related pathology, we investigated hippocampal tissue of 15 major-depressed patients, 16 matched controls, and 9 steroid-treated patients, using in situ-end-labeling for DNA fragmentation and apoptosis, and heat-shock protein 70 and nuclear transcription factor κB immunocytochemistry for damage-related responses. No obvious massive cell loss was observed in any group. In 11 of 15 depressed patients, rare, but convincing apoptosis was found in entorhinal cortex, subiculum, dentate gyrus, CA1, and CA4. Also in three steroid-treated patients, apoptosis was found. Except for several steroid-treated patients, heat-shock protein 70 staining was generally absent, nor was nuclear transcription factor-κB activation found. The detection in 11 of 15 depressed patients, in three steroid-treated, and in one control patient, demonstrates for the first time that apoptosis is involved in steroid-related changes in the human hippocampus. However, in absence of major pyramidal loss, its rare occurrence, that notably was absent from areas at risk for GC damage such as CA3, indicates that apoptosis probably only contributes to a minor extent to the volume changes in depression.

Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure

Sex differences in estrogen receptor α and β expression in vasopressin neurons of the supraoptic nucleus in elderly and Alzheimer’s disease patients: no relationship with cytoskeletal alterations

We report here the recognition of a new distinctive small group of patients within the spectrum of frontotemporal dementia (FTD) pathology. We present three cases with the clinical diagnosis of frontotemporal dementia (FTD) and neuropathological changes restricted to the medial temporal lobe. The presenting symptoms of these cases were family history of dementia in two of the three cases (two sisters), agitation, apathy, dysphasia, and memory problems. Two of the three cases were clinically diagnosed as Pick’s disease and the third with probable Alzheimer’s disease. Pathologically, they resemble cases reported with hippocampal sclerosis, and ubiquinated inclusions were present in the hippocampus and ventral striatum. Our observations support the existence of a subgroup; we propose to call the cases with distinctive pathology as described in the present paper “Pick D”, as they may be a restricted group who resemble PickC1 according to the division proposed by Constantinidis within Pick’s disease.

Exclusive Mediotemporal Pathology Within the Spectrum of Frontotemporal Dementia

Coordinated evaluation of astrogliosis, microglial activation and proliferation in the Alzheimer hippocampus in relation to cognitive status and amyloid pathology

Jose Wouda

Papers

Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure

Sex differences in estrogen receptor α and β expression in vasopressin neurons of the supraoptic nucleus in elderly and Alzheimer’s disease patients: no relationship with cytoskeletal alterations

Exclusive Mediotemporal Pathology Within the Spectrum of Frontotemporal Dementia

Coordinated evaluation of astrogliosis, microglial activation and proliferation in the Alzheimer hippocampus in relation to cognitive status and amyloid pathology