Glucocorticoids Orchestrate Adult Hippocampal Plasticity: Growth Points and Translational Aspects

Abstract

The review analyzes modern concepts about the control of various mechanisms of the hippocampal neuroplasticity in adult mammals and humans by glucocorticoids. Glucocorticoid hormones ensure the coordinated functioning of key components and mechanisms of hippocampal plasticity: neurogenesis, glutamatergic neurotransmission, microglia and astrocytes, systems of neurotrophic factors, neuroinflammation, proteases, metabolic hormones, neurosteroids. Regulatory mechanisms are diverse; along with the direct action of glucocorticoids through their receptors, there are conciliated glucocorticoid-dependent effects, as well as numerous interactions between various systems and components. Despite the fact that many connections in this complex regulatory scheme have not yet been established, the study of the factors and mechanisms considered in the work forms growth points in the field of glucocorticoid-regulated processes in the brain and primarily in the hippocampus. These studies are fundamentally important for the translation into the clinic and the potential treatment/prevention of common diseases of the emotional and cognitive spheres and respective comorbid conditions.

An Interaction between Brain-Derived Neurotrophic Factor and Stress-Related Glucocorticoids in the Pathophysiology of Alzheimer’s Disease

“…In addition, in adult mammals and humans, it has been demonstrated that neuroplasticity, which is controlled through various mechanisms, is influenced by GC stress. As expected, regulated levels of blood GCs are closely associated with brain function by affecting hippocampal plasticity, including glutamatergic neurotransmission, neurogenesis, systems of neurotrophic factors, microglia, astrocytes, neuroinflammation, and so on [35]. In addition to the amygdala and hippocampus, the prefrontal cortices are involved in the corticolimbic system and are perturbed by the abnormal function of BDNF/TrkB-related signaling and activity of GR [36].…”

Ambiguous Contribution of Glucocorticosteroids to Acute Neuroinflammation in the Hippocampus of Rat

“…Our results suggest that the GCS ambiguously modulate specific aspects of neuroinflammatory response in the hippocampus on both molecular and cellular levels. Directly or indirectly, both GCS and neuroinflammatory processes are involved in virtually all mechanisms of hippocampal neuroplasticity [ 30 ], and the routes of this control by GCS are obviously much more intricate than what we can hypothesize based on available but yet obviously incomplete experimental data.…”

Early Adverse Family Experiences and Elevated Adrenocorticotropic Hormone Predict Non-Suicidal Self-Injury in Females with Non-Psychotic Mental Disorders and Suicidal Ideation

“…Glucocorticoids, executive hormones of HPA axis ensure the coordinated functioning of key components and mechanisms of brain plasticity at different levels, including neurogenesis, glutamatergic neurotransmission, microglia and astrocytes, systems of neurotrophic factors, neuroinflammation, etc. [69]. Adaptation to chronic hyperactivation of the HPA axis may lead to loss of the system sensitivity through chronic activation of negative feedback and feed-forward regulators.…”