Stress effects on the hippocampus: a critical review

Abstract

Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal neurons. Structurally, human and animal studies have shown that stress changes neuronal morphology, suppresses neuronal proliferation, and reduces hippocampal volume. Since the inception of stress research nearly 80 years ago, much focus has been on the varying levels of hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine hormones, namely glucocorticoids, as mediators of the myriad stress effects on the hippocampus and as contributing factors to stress-associated psychopathologies such as post-traumatic stress disorder (PTSD). However, reports of glucocorticoid-produced alterations in hippocampal functioning vary widely across studies. This review provides a brief history of stress research, examines how the glucocorticoid hypothesis emerged and guides contemporary stress research, and considers alternative approaches to understanding the mechanisms underlying stress effects on hippocampal functioning.

Moderate Stress-Induced Social Bonding and Oxytocin Signaling are Disrupted by Predator Odor in Male Rats

“…Our results are in agreement with studies showing that similar CORT elevations can drive either positive and negative outcomes (eg, in cognitive function and performance) based on the psychological context in which the stress is experienced (reviewed in (Kim et al, 2015)). …”

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“…Hippocampus of the brain provides negative control over the HPA axis. Chronic Stress suppresses cell proliferation in the hippocampus 17 and leads to the activation of the HPA axis 18 . A stressful signal stimulates secretion of Corticotropin Releasing Factor (CRF) 19 .…”

Deletion of novel protein TMEM35 alters stress-related functions and impairs long-term memory in mice

“…Furthermore, HPA output is able to modulate the normal functions of these regions and, thereby, alter behaviors associated with the limbic circuitry-namely, affective behavior, as well as learning and memory (22,47,69). For instance, a disruption of normal HPA activity, resulting from extreme or unpredictable stress, can lead to increased anxiety and memory deficits (22,31,32,36,54) and contribute to affective disorders, including post-traumatic stress disorder (PTSD) and depression (10, 50).Extensive investigations into the mechanisms of plasticity within the HPA-limbic circuitry have identified roles for several key molecules, including brain-derived neurotrophic factor (BDNF) and the glucocorticoid receptor (GR) (1,21,63,69). However, our knowledge of the complement of molecules regulating plasticity of this network remains incomplete (9, 13, 56), underscoring a need for additional investigation of novel candidates expressed within this circuitry.…”

“…Although HPA activity is normally selfregulated by negative feedback via glucocorticoid stress hormone acting in the hypothalamus, additional regulation occurs through input from limbic areas, including the amygdala and hippocampus (21,23). Furthermore, HPA output is able to modulate the normal functions of these regions and, thereby, alter behaviors associated with the limbic circuitry-namely, affective behavior, as well as learning and memory (22,47,69). For instance, a disruption of normal HPA activity, resulting from extreme or unpredictable stress, can lead to increased anxiety and memory deficits (22,31,32,36,54) and contribute to affective disorders, including post-traumatic stress disorder (PTSD) and depression (10,50).…”