The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: Implications for hippocampal volume reductions in depression

Abstract

Glucocorticoids (GCs) are hormones secreted by the adrenal glands as an endocrine response to stress. Although the main purpose of GCs is to restore homeostasis when acutely elevated, animal studies indicate that chronic exposure to these hormones can cause damage to the hippocampus. This is indicated by reductions in hippocampal volume, and changes in neuronal morphology (i.e.., decreases in dendritic length and number of dendritic branch points) and ultrastructure (e.g., smaller synapse number). Smaller hippocampal volume has been also reported in humans diagnosed with major depressive disorder or Cushing's disorder, conditions in which GCs are endogenously and chronically elevated. Although a number of studies considered neuron loss as the major factor contributing to the volume reduction, recent findings indicated that this is not the case. Instead, alterations in dendritic, synaptic and glial processes have been reported. The focus of this paper is to review the GCs effects on the cell number, dendritic morphology and synapses in an effort to better understand how these changes may contribute to reductions in hippocampal volume. Taken together, the data from animal models suggests that hippocampal volumetric reductions represent volume loss in the neuropil, which, in turn, under represent much larger losses of dendrites and synapses.

H<sub>2</sub>S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway

“…Hypothalamic-pituitary-adrenal (HPA) axis was found to respond to stress, and particularly its hyperactivity is a key feature of depression [5]. The durable increases in glucocorticoids (corticosterone in rodents, cortisol in humans) which are the endpoint of HPA axis activation mainly mediate the influence of repeated or chronic stress in animal models as well as in humans [6,7]. The elevation of corticosterone induced by stressors may be closely associated with the development of depression [8].…”

MANAGEMENT OF ENDOCRINE DISEASE: Cushing's syndrome: a structured short- and long-term management plan for patients in remission

“…In rodents, short-term GC administration leads to atrophy of dendrites in hippocampal neurons, changes that are reversible when GCs are withdrawn (66). Longer exposure to high GC levels causes hippocampal degeneration, partly due to loss of neurons (66). These observations support that the cognitive dysfunction observed in patients with CS may be caused by irreversible changes in the CNS.…”

“…During states of GC excess, the protective role of 11b-HSD2 is therefore absent, and areas that express GC and mineralocorticoid receptors abundantly, such as the limbic system, may therefore be especially vulnerable. In rodents, short-term GC administration leads to atrophy of dendrites in hippocampal neurons, changes that are reversible when GCs are withdrawn (66). Longer exposure to high GC levels causes hippocampal degeneration, partly due to loss of neurons (66).…”

Hippocampal Volume in Type 1 Diabetes

“…59 63 however, in an adolescent population, these two factors were not associated which may indicate age-dependent effects from chronic exposure to hyperglycemia on the hippocampus. 62 Animal models suggest that chronic hyperglycemia can reduce the complexity of neuronal dendrites and dendritic spines 54 and damaging these neuronal processes could lead to a smaller hippocampal volume, 46 but developing adolescents might be able to overcome this loss due to the presence of growth factors or other developmentally regulated molecules.…”