Chronic systemic Ang-(1-7) administration significantly increased the novel object preference index in aged mice compared to saline (73% vs 49%, p<0.001), improving learning and memory.
Does Angiotensin-(1-7) improve learning and memory in aged mice?
Chronic systemic Ang-(1-7) administration improves learning and memory and supports hippocampal long-term potentiation in aged mice.
Absolute Event Rate: 73% vs 49%
p-value: p=<0.001
Cognitive decline, including impairments in learning and memory, is a normal part of the aging process. Several peripheral and central mechanisms are known to contribute to age-related cognitive decline, including vascular dysfunction, insulin resistance, blood-brain barrier disruption, and neuroinflammation. More recently, dysfunction of the renin-angiotensin system (RAS), characterized by increased angiotensin (Ang) II activity and decreased Ang-(1-7) activity, has been implicated in cognitive decline in both healthy aging and neurocognitive disorders. In terms of healthy aging, a recent study from our laboratory showed that chronic Ang-(1-7) treatment decreases blood pressure and improves glucose homeostasis in aged mice. Whether Ang-(1-7) can also ameliorate the cognitive decline observed with aging in this model, however, has not been investigated. Therefore, in this study, we hypothesized that chronic systemic Ang-(1-7) administration improves cognition in healthy aged mice. To test this, sixteen month-old male C57Bl/6J and two month-old young mice were implanted with subcutaneous osmotic mini-pumps and treated with either Ang-(1-7) 400 ng/kg/min; young Ang-(1-7) n=8, aged Ang-(1-7) n=11 or saline (young saline n= 9; aged saline n=11) for six weeks. At the end of treatment, a novel object recognition test was conducted to assess learning and memory. As expected, we found that aged saline mice exhibited a decrease in the novel object preference index compared to young saline mice (49±1% vs. 66±2%, respectively; p< 0.001), consistent with impaired age-related learning and memory. Ang-(1-7) significantly increased the novel object preference index in aged mice (73±3%, p< 0.001 vs. aged saline), to the level seen in young saline-treated mice, with similar effects on the novel object discrimination index and exploration time. Ang-(1-7) did not affect the novel object preference index, discrimination index, or exploration time in young mice. Brains were collected from a subset of aged mice treated with Ang-(1-7) or saline (n=4 per group) to examine long-term potentiation (LTP) of excitatory postsynaptic potentials (fEPSP) in hippocampal CA1 slices. Theta burst stimulation of Schaeffer collateral inputs to CA1 was unable to induce LTP in aged saline-treated mice but induced LTP in aged Ang-(1-7)-treated mice (67.7±20.3 vs. 161.1±28.8% of baseline, respectively; p=0.038). Together, these findings suggest that Ang-(1-7) improves learning and memory in aged mice as well as supports maintenance of LTP in the hippocampus. This study was supported by NIH Grant K99 HL159272. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
tanner et al. (Fri,) conducted a other in Age-related cognitive decline (n=39). Angiotensin-(1-7) vs. Saline was evaluated on Novel object preference index in aged mice (p=<0.001). Chronic systemic Ang-(1-7) administration significantly increased the novel object preference index in aged mice compared to saline (73% vs 49%, p<0.001), improving learning and memory.