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

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.

Figure 1.

Stress causes body weight alterations at all ages. A, In 3-month-old rats, stress reduced weight gain over the course of the paradigm, which normalized with 3 weeks of recovery. B, In 12-month-old rats, stress caused weight loss that normalized with recovery. C, In 20-month-old rats, stress caused robust weight loss that did not normalize with 3 weeks of recovery. ***p < 0.001, control versus stress; ^††p < 0.005, stress versus recovery; ^†††p < 0.001, stress versus recovery; ^###p < 0.001, control versus recovery. Data presented represent group mean ± SEM.

Figure 2.

Neuronal reconstructions. A, Anatomical localization of rat PL cortex. Adapted from Paxinos and Watson (2005). B, A deconvolved confocal image of a Lucifer yellow-filled layer III PL pyramidal neuron. C, A manual reconstruction of the same neuron. Pial surface of the PL cortex is to the right.

Figure 3.

Aging reduces the capacity for reversible apical dendritic remodeling in response to stress. A–C, Stress caused alterations in apical dendritic morphology that were entirely reversible with recovery in young rats. D–F, Stress caused alterations in apical dendritic morphology that were only partially reversible with recovery in middle-aged rats. G–I, Stress caused alterations in apical dendritic morphology that were not reversible with recovery in aged rats. *p < 0.05; **p < 0.01; and ***p < 0.001, control versus stress. ^†p < 0.05 and ^†††p < 0.001, stress versus recovery. ^#p < 0.05; ^##p < 0.01; and ^###p < 0.001, control versus recovery. Data presented represent group mean ± SEM.