Clinically relevant hormone treatments fail to induce spinogenesis in prefrontal cortex of aged female rhesus monkeys.

Preclinical animal models have provided strong evidence that estrogen (E) therapy (ET) enhances cognition and induces spinogenesis in neuronal circuits. However, clinical studies have been inconsistent, with some studies revealing adverse effects of ET, including an increased risk of dementia. In an effort to bridge this disconnect between the preclinical and clinical data, we have developed a nonhuman primate (NHP) model of ET combined with high-resolution dendritic spine analysis of dorsolateral prefrontal cortical (dlPFC) neurons.

Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex.

Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, nonhuman primates, and rodents, although the neurobiological correlates of this vulnerability remain largely unknown. It has been proposed that dendritic spines represent the primary site of structural plasticity in the adult brain, and recent data have supported the hypothesis that aging is associated with alterations of dendritic spine morphology and plasticity in prefrontal cortex. However, no study to date has directly examined whether aging alters the capacity for experience-dependent spine plasticity in aging prefrontal neurons.