Many treatment initiatives, like herbal products and their active ingredients, aim to alleviate neurodegeneration to increase cognitive functions. Kaempferol may be a candidate molecule for treating neurodegeneration because of its antioxidant effects. In the present study, we examined the molecular changes associated with kaempferol’s memory‑enhancing effects on streptozotocin (STZ)‑induced neurodegeneration. After intracerebroventricular STZ injection in Long‑Evans male rats, intraperitoneal kaempferol was administered for 12 days. The Morris water maze (MWM) was used to measure learning and memory performance in the rats, and proteins related to memory formation were investigated in the hippocampi with western blotting. Kaempferol improved learning performance and memory decline in STZ‑treated rats. At the molecular level, STZ‑induced neurodegeneration resulted in a decrease in the expression of GAD67, reelin, and phosphorylated‑NMDAR. However, kaempferol treatment ameliorated these changes by enhancing their levels similar to the controls. While neither STZ injection nor kaempferol treatment produced any significant change in phosphorylated‑CAMKII levels, they increased the expression of klotho and prealbumin. These results show that kaempferol has positive effects on memory loss, affecting synaptic plasticity by ameliorating both the levels and activity of memory‑relevant molecules through reelin signaling. In summary, this study provides a guide to future studies by examining in detail the healing effect of kaempferol as a candidate molecule in the treatment of neurodegeneration, such as that observed in Alzheimer’s disease.
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