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: 6.34). 05/2010; 30(19):6726-31. DOI: 10.1523/JNEUROSCI.0759-10.2010
Source: PubMed


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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    • "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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    • "As in the hippocampus, this plasticity is driven by glucocorticoids (Cerqueira et al 2005) in concert with excitatory amino acids (Martin & Wellman 2011). With increasing age, while the effects of stress to cause dendritic shortening and debranching persist, the spontaneous recovery within 3 weeks after the cessation of chronic stress is diminished in 12 month old rats and lost in 20 month old animals (Bloss et al 2010). Moreover, there is loss of thin spines in the mPFC neurons by 12 months of age and a loss of the ability of chronic stress to cause further significant reduction of spines (Bloss et al 2011). "
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