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. 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.
Fishberg Department of Neuroscience, The Friedman Brain Institute, Kastor Neurobiology of Aging Laboratory, Mount Sinai School of Medicine, New York, New York 10029, USA.
Daniel T
DT
Ohm
Erik B
EB
Bloss
William G
WG
Janssen
Karen C
KC
Dietz
Shannon
S
Wadsworth
Wendy
W
Lou
Nancy A
NA
Gee
Bill L
BL
Lasley
Peter R
PR
Rapp
John H
JH
Morrison
D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects*; D004967:Estrogens / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010052:Ovariectomy; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*
D004967:Estrogens; D011374:Progesterone