Background: Hypothyroidism is an endocrine disorder characterized by reduced thyroid hormone production, leading to impaired neuronal excitability and calcium signaling.

Objective: This study investigates the corrective effect of polyphenol R-1 on calcium-dependent mechanisms of neuronal activity under experimental hypothyroidism.

Methods: Hypothyroidism was induced in male outbred rats (220–250 g) by oral administration of mercazolil (2.5 mg/100 g) for 21 days. Behavioral, biochemical, and synaptosomal calcium changes were evaluated. Calcium concentrations were measured using Fluo-4 AM fluorescence on a USB 2000 spectrofluorimeter. Polyphenol R-4 (50 mg/kg, intraperitoneal) was administered for 10 days after hypothyroidism induction.

Results: Hypothyroid rats showed lethargy, reduced exploratory activity, decreased T3/T4 levels, elevated TSH, and diminished intracellular [Ca²⁺]in synaptosomes. Treatment with R-4 significantly normalized these changes, restoring calcium levels, metabolic parameters, and cognitive behavior.

Conclusion: Polyphenol R-4 demonstrates a neuroprotective effect by stabilizing calcium homeostasis through modulation of NMDA receptor and VGCC activity, suggesting its potential as a pharmacological regulator of calcium signaling in hypothyroid-associated neurodegeneration.

Hypothyroidism, polyphenol R-4, synaptosomes

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