Читать книгу The Science of Health Disparities Research - Группа авторов - Страница 33

A critically significant adaptive function for promoting and maintaining survival is the memory system. The active process of recollection and embedding of past adverse experiences provides a means of assuring that similar events can be appropriately avoided or circumnavigated. The release of glucocorticoids through the HPA axis in response to stress also influences pathways and mechanisms that govern multiple aspects of memory [15]. Cortisol has access to many areas of the brain that express both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) [9]. While GRs are ubiquitous throughout the brain, MRs are mostly concentrated in the limbic regions, including the hippocampus and the amygdala. GR activation is associated with consolidation, the transition of short‐term to long‐term memory. MR activation is associated with evaluation and response to stressful experiences.

Research indicates that glucocorticoids have complicated influences on memory consolidation and retrieval. Moreover, chronic elevation of glucocorticoid in combination with NE has a strong influence on neurogenesis through their influence on neuronal plasticity by promoting dendritic remodeling at the cellular level [5]. Such influences are complex and sometimes paradoxical. While glucocorticoids play a role in the consolidation of memory of emotionally arousing experiences, they can also impair retrieval of primary learned or memorized events. Learning and memory processes take place in complex networks of regions in the brain that may act in parallel or competition. Studies suggest that emotional stress can promote rerouting of systems of memory and learning.

For example, new findings have demonstrated that stress can create a shift in the hippocampal cognitive learning to “reflexive” stimulus‐response or habitual learning governed through the dorsal striatum (DR) (Figure 2.4). A role for the amygdala in mediating this switch has been suggested [15]. The activation of stress pathways in the regulation of emotional memory is highly adaptive and important for survival. However, its chronic activation occurs at the cost of an “allostatic load,” which becomes the underlying cause of emotional conditions or disease characterized by fear, anxiety, depression, and post‐traumatic stress disorders. The hippocampus is a central region controlling disorders of mood, including anxiety and depression [16]. Patients with major depression develop hippocampal atrophy [17]. The neuronal population within the hippocampus is maintained by a population of neural progenitors that are exquisitely sensitive to glucocorticoids [18, 19]. In experimental systems, excess glucocorticoid exposure has been associated with decreased neuronal growth and differentiation and increased cell death in the hippocampus [16, 18, 20, 21]. An example of this “cost” of chronically elevated cortisol level is well documented by the mood disorders associated with patients suffering from Cushing syndrome, a condition characterized by high levels of cortisol due to chronic activation of the HPA by a pituitary tumor [20].

Figure 2.4 Schematic diagram of the influence of glucocorticoids and stress on memory, learning, and mood. T2DM, Type 2 diabetes mellitus; PTSD, post‐traumatic stress syndrome.