Interactive effects of stress and aging on structural plasticity in the prefrontal cortex

Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, New York 10029, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 05/2010; 30(19):6726-31. DOI: 10.1523/JNEUROSCI.0759-10.2010
Source: PubMed

ABSTRACT Neuronal networks in the prefrontal cortex mediate the highest levels of cognitive processing and decision making, and the capacity to perform these functions is among the cognitive features most vulnerable to aging. Despite much research, the neurobiological basis of age-related compromised prefrontal function remains elusive. Many investigators have hypothesized that exposure to stress may accelerate cognitive aging, though few studies have directly tested this hypothesis and even fewer have investigated a neuronal basis for such effects. It is known that in young animals, stress causes morphological remodeling of prefrontal pyramidal neurons that is reversible. The present studies sought to determine whether age influences the reversibility of stress-induced morphological plasticity in rat prefrontal neurons. We hypothesized that neocortical structural resilience is compromised in normal aging. To directly test this hypothesis we used a well characterized chronic restraint stress paradigm, with an additional group allowed to recover from the stress paradigm, in 3-, 12-, and 20-month-old male rats. In young animals, stress induced reductions of apical dendritic length and branch number, which were reversed with recovery; in contrast, middle-aged and aged rats failed to show reversible morphological remodeling when subjected to the same stress and recovery paradigm. The data presented here provide evidence that aging is accompanied by selective impairments in long-term neocortical morphological plasticity.

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    • "It is also noteworthy that hippocampal volume increases with intense learning (Draganski et al. 2006), but is also decreased in Cushing's disease (Starkman et al. 1992). However, there is age-related loss of resilience of the dendrite shrinkage in prefrontal cortex (Bloss et al. 2010), as well as age-related memory impairment, which, however, can be reduced by pharmacological intervention (Bloss et al. 2008, Pereira et al. 2014). These treatments may find their way into treating human mild cognitive impairment and perhaps also dementia. "
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    ABSTRACT: The discovery of steroid hormone receptors in brain regions that mediate every aspect of brain function has broadened the definition of "neuroendocrinology" to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive. But, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic anxiety and depression. There are important sex differences in the brain responses to stressors that are in urgent need of further exploration. Moreover, adverse early-life experience, interacting with alleles of certain genes, produce lasting effects on brain and body over the life-course via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain-body interactions.
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    • "The changes in neural and behavioural measures brought about by chronic stress in the hippocampus and medial prefrontal cortex, but perhaps not the amygdala (Conrad et al., 1999; Vyas et al., 2004), are reversible with time (Bian et al., 2012; Dagyte et al., 2009; Heine et al., 2004; Radley et al., 2005; Sousa et al., 2000) or with new learning (Sandi et al., 2003). The capacity to recover from chronic stress, however, may diminish with advanced age (Bloss et al., 2010). The findings above involved investigations in male mice and rats, although similar results have been found for stressors in other species [e.g., hamsters, (Walton et al., 2012); tree shrews, (Fuchs et al., 2001); humans (Qin et al., 2012)]. "
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    ABSTRACT: This article is part of a Special Issue "Puberty and Adolescence". Learning and memory is affected by a myriad of factors, including exposure to stressors and the corresponding rise in circulating glucocorticoids. Nevertheless, the effects of stressors depend on the sex, species, the type of stressor used, the duration of exposure, as well as the developmental time-point in which stressors are experienced. Effects of stress in adolescence, however, have received less attention than other developmental periods. In adolescence, the hypothalamic-pituitary-adrenal axis and brain regions involved in learning and memory, which also richly express corticosteroid receptors, are continuing to develop, and thus the effects of stress exposures would be expected to differ from those in adulthood. We conclude from a review of the available literature in animal models that hippocampal function is particularly sensitive to adolescent stressors, and the effects tend to be most evident several weeks after the exposure, suggesting stressors alter the developmental trajectory of the hippocampus.
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    • "Importantly, the stress-induced impairment of PIT was no longer evident after a stress-free period. This reversibility of stress effects is in accordance with previous studies showing the recovery of other stress-induced deficits, including spatial memory (Sousa et al., 2000), and behavioral flexibility (Bloss et al., 2010), after similar stress-free periods. Of note, recovery of these functions is paralleled by synaptic regrowth and reorganization on the hippocampus and the mPFC, which are also involved in PIT. "
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