Rotenone-Induced Dysregulation of Synaptosomal Ca²⁺ And Hypokinetic Behavior in A Rat Model of Parkinsonism
Keywords:
Parkinsonism, rotenone, synaptosomesAbstract
Background: Rotenone, a lipophilic mitochondrial complex I inhibitor, is widely used to model Parkinsonian neurodegeneration and synaptic failure.
Objective: To quantify rotenone-associated behavioral changes and determine whether they co-occur with altered glutamate-evoked synaptosomal Ca²⁺ dynamics.
Methods: Adult male Wistar rats were randomized into control and rotenone groups (2.5 mg/kg/day, i.p., 11 consecutive days; n=6/group). Exploratory behavior was assessed in an open-field/hole-board ar ena (42 × 42 cm; 42-floor grid; 3 min; ~100 lux). Crude synaptosomes (P2 fraction) were isolated from whole brain tissue, loaded with Fluo‑4AM (final 5 µM, 30 min, 37°C), and stimulated with L‑glutamate (50 µM). Ca²⁺ responses were summarized as resting signal, peak amplitude, area under the curve (AUC), and clearance time constant (τ).
Results: Rotenone reduced horizontal locomotion (72±6 vs 14±4 crossings), vertical activity (38±5 vs 8±3 rearings), and hole‑poking (16±2 vs 6±1; all p<0.05). Synaptosomes from rotenone-treated rats displayed a higher resting Ca²⁺-related fluorescence (+21%) and enhanced glutamate-evoked Ca²⁺ responses (peak +18%, AUC +25%), alongside faster decay (τ −17%) relative to controls (p<0.05).
Conclusions: Subchronic rotenone exposure produces a reproducible hypokinetic phenotype that parallels presynaptic Ca²⁺ dysregulation, supporting a mechanistic link between mitochondrial stress and abnormal glutamate-triggered Ca²⁺ signaling.
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Copyright (c) 2026 Zayniyeva Makhbuba, Izzatillaeva Sabina, Tajiyeva Oyimjan, Kоzоkоv Islom, Dеdаbоеv Jobir, Mukhtоrоv Alisher, Khоshimоv Nozim
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