Motor dysfunction and alterations in glutathione concentration, cholinesterase activity, and BDNF expression in substantia nigra pars compacta in rats with pedunculopontine lesion

- PPN unilateral neurotoxic lesion produces fine motor dysfunction in rats.
- Beam and footprint tests are useful to evaluate subtle motor dysfunction in rats.
- PPN neurotoxic lesion modifies GSH concentration, EA AChE and BDNF expression in nigral tissue.
- PPN unilateral neurotoxic lesion modifies the redox balance in SNpc.
- The unilateral PPN neurotoxic lesion may compromise their role in motor control.

Pedunculopontine nucleus (PPN) has been considered a critically important region in the regulation of some of the physiological functions that fail during the progression of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN [through the injection of N-methyl-d-aspartate (NMDA) solution (concentration: 0.1 M; volume: 0.5 µL)] in motor execution and gait disorders and the changes in cellular and molecular indicators in rat nigral tissue were evaluated. The motor execution was assessed using the beam test (BT) and the gait disorders by footprint test. Glutathione (GSH) concentrations, acetyl cholinesterase enzymatic activity (AChE EA), and brain-derived neurotrophic factor (BDNF) mRNA expression in nigral tissue were analyzed. NMDA-lesioned rats showed fine motor dysfunction with a significant increase in the slow (p ≤ 0.01) and fast movement (p ≤ 0.01) time and in path deviation (p ≤ 0.01) on the smaller diameter beams. Moreover, NMDA-lesioned rats exhibited an imprecise path with moments of advances and setbacks, alternating with left and right deviations, suspensions, and inverted positions. Footprint test revealed slight gait disorders, which were manifested by a reduction in the left and right stride lengths, the intra-step distance, and the support area (p ≤ 0.01). Biochemical studies showed that 48 h after the PPN neurotoxic injury, the GSH concentrations and BDNF expression were significantly increased (p ≤ 0.01). These variables returned to normal values 7 days after the PPN lesion; the AChE EA showed a significant increase at this time. These functional changes in nigral tissue could be a plastic responses associated with early PD.