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Neurodegenerative disease, such as alzheimer, demensia, and parkinson, is a non communicable disease where the central nervous system including its cells stopped working in an individual. The prevalence of neurodegenerative disease has been continued to increase in number every year throughout the world. In Indonesia, the society believed many plants can act as a herbal medicine, which one of those are nutmeg, a seed which often used by elder people. Previous study showed nutmeg can increase the activity of peroxisome proliferator activated receptors γ (PPAR-γ) which might increase synaptic plasticity.In this study, we would like to explore the potential of nutmeg in maintaining synaptic plasticity in synaptic vesicles. Rats aged 10-11 weeks old were divided into two groups, the nutmeg and the control. Treatment were given to the rats by gavaging nutmeg extract daily for 12 weeks. When treatment was done, rats were anesthetized in order to take part of their cerebral cortex from the brain and stored in frozen storage at -80º C. Our present study showed nutmeg extract increased the activity of synaptic plasticity in a significant manner through the expression of synapsin, synaptophysin, and BDNF gene. Nutmeg extract acted as a ligand that activates PGC1-α, stimulates transmission in vesicles, and opens transmitter doors swiftly. This research may proves the potential of nutmeg extract as a supplement to prevent neurodegenerative disease in elderly people.