Circulating oxytocin levels are known to decline with age, and a number of research groups have focused on upregulation of oxytocin as an approach to treating aging. A couple of papers published a few months ago are indicative of the animal studies presently taking place, the first focused on increased longevity in mice achieved via the combined reduction of TGF-β and increase in oxytocin, and the second evaluating intranasal delivery of oxytoxin as a route to improve function in the aging brain.
Today’s paper reports on another example of oxytocin delivery in aged mice. These researchers are also focused on the brain, but in this case the oxytocin is delivered via intraperitoneal injection. As with most peptide or protein therapies, the effects are limited in scope as the delivered molecules have a short half-life. Repeated treatments are required, often daily, as is the case here. Given further progress towards the clinic, however, we might expect that the community of developers presently assessing gene therapies to safely transform a small number of cells into long-lasting factories that produce a desired circulating molecule (such as klotho or follistatin) will add oxytocin to their list.
Brain aging is characterized by progressive structural and functional deterioration, leading to cognitive decline and impaired social functioning. A key factor in this process is the age-related decline in adult neurogenesis, particularly in the hippocampal dentate gyrus, which is linked to deficits in learning, memory, and increased social anxiety. Oxytocin, a neuropeptide synthesized in the hypothalamus, regulates social behavior, cognition, and emotion by acting on brain regions including the hippocampus. Importantly, oxytocin levels decrease with age, potentially contributing to cognitive impairment.
Here, we examined whether chronic intraperitoneal oxytocin administration could attenuate cognitive decline in aged mice. Twelve-month-old mice received oxytocin injections (0.5 mg/kg) five times weekly for 13 weeks. Behavioral testing at 12 weeks of treatment using the object-place recognition task showed enhanced spatial learning and recognition memory in oxytocin-treated mice compared with saline controls. Immunohistochemistry revealed significantly increased doublecortin (DCX)-positive cells in the hippocampus, indicating enhanced neurogenesis. Furthermore, oxytocin treatment upregulated the expression of glutamate receptor 1 (GluR1) and N-methyl-D-aspartate receptor subunit 2B (NMDAR2B), which are markers of synaptic plasticity.
These findings suggest that chronic oxytocin treatment is associated with enhanced neurogenesis and synaptic plasticity, which may contribute to improved cognition in aged mice. Our results support oxytocin as a potential therapeutic agent for age-related cognitive decline.
