Behavioral and Synaptosomal Fluorescence Effects of Polyphenol in Hypothyroid Rats

Hypothyroidism alters behavior, endocrine homeostasis, and synaptic physiology in man and animals, yet presynaptic calciumassociated endpoints remain incompletely characterized.This study evaluated whether R-4, a Rhus glabra-derived polyphenolrich fraction, modulates endocrine, behavioral, biochemical, and synaptosomal calcium-associated responses in methimazoletreated rats.Adult male rats were assigned to control, hypothyroid, and hypothyroid + R-4 groups (n = 6 each).Hypothyroidism was induced with methimazole (2.5 mg/100 g/day, intragastrically) for 21 days, while R-4 was administered orally (50 mg/kg/day) during days 12-21.Open-field behavior, thyroid ultrasonography, serum thyroid hormones, serum and whole-brain biochemistry, synaptosome isolation, and Fluo-4-based fluorescence were assessed.Methimazole reduced T3, increased TSH, enlarged the thyroid gland, suppressed exploratory activity, and lowered basal synaptosomal Fluo-4-associated fluorescence relative to controls.R-4 partially normalized selected serum indices, improved exploratory behavior, and increased the reduced synaptosomal fluorescence signal in preparations from hypothyroid rats.The R-4-associated fluorescence response was attenuated under NMDA-related and voltage-gated Ca 2+-linked conditions, suggesting participation of both signaling domains.Because the readout was based on normalized Fluo-4 fluorescence rather than calibrated absolute [Ca 2+ ]i, the findings are interpreted as an altered synaptosomal calcium-associated fluorescence phenotype.Overall, the plant-derived Rhus glabra fraction behaved as a rapid synaptosome-level modulator in experimental hypothyroidism and supports further evaluation of plant bioactives in applied animal physiology.