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

Daniel T. Ohm, Erik B. Bloss, William G. Janssen, Karen C. Dietz, Shannon Wadsworth, Wendy Lou, Nancy A. Gee, Bill L. Lasley, Peter R. Rapp, John Morrison

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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. Previously, we reported cyclic ET in aged, ovariectomized NHPs increased spine density on dlPFC neurons. Here, we report that monkeys treated with cyclic E treatment paired with cyclic progesterone (P), continuous E combined with P (either cyclic or continuous), or unopposed continuous E failed to increase spines on dlPFC neurons. Given that the most prevalent form of ET prescribed to women is a combined and continuous E and P, these data bring into convergence the human neuropsychological findings and preclinical neurobiological evidence that standard hormone therapy in women is unlikely to yield the synaptic benefit presumed to underlie the cognitive enhancement reported in animal models.

Original languageEnglish (US)
Pages (from-to)11700-11705
Number of pages6
JournalJournal of Neuroscience
Volume32
Issue number34
DOIs
StatePublished - Aug 22 2012
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ohm, D. T., Bloss, E. B., Janssen, W. G., Dietz, K. C., Wadsworth, S., Lou, W., Gee, N. A., Lasley, B. L., Rapp, P. R., & Morrison, J. (2012). Clinically relevant hormone treatments fail to induce spinogenesis in prefrontal cortex of aged female rhesus monkeys. Journal of Neuroscience, 32(34), 11700-11705. https://doi.org/10.1523/JNEUROSCI.1881-12.2012