Motor Coordination Disorders Evaluated through the Grid Test and Changes in the Nigral Nrf2 mRNA Expression in Rats with Pedunculopontine Lesion

Abstract

Neurotoxic lesion of the pedunculopontine nucleus (PPN) is known to cause subtle motor dysfunctions. However, motor coordination during advance on a discontinuous and elevated surface has not been studied. It is also not known whether there are changes in the mRNA expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in nigral tissue. Methods: The effects of the unilateral neurotoxic lesion of the PPN in motor coordination evaluated through grid test and Nrf2 mRNA expression in nigral tissue were evaluated. Two experimental designs (ED) were organized: ED#1 behavioral study (7 and 30 days after PPN lesion) and ED#2 molecular biology study (24 h, 48 h and 7 days) after PPN lesion. Results: ED#1—The number of faults made with left limbs, were significant higher in the lesioned groups (p < 0.01) both 7 and 30 days post-lesion. The number of failures made by the right limbs, was also significantly higher (p < 0.05) vs. control groups. ED#2—Nrf2 mRNA expression showed an increase 24 h after PPN injury (p < 0.01), followed by a peak of expression 48 h post injury (p < 0.001). Conclusions: Disorders of motor coordination associated with PPN injury are bilateral. The increased Nrf2 mRNA expression could represent an adaptive response to oxidative stress in the nigral tissue following pontine injury.

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“…In the cellular and molecular scenario proposed by our work, there is no significant loss of cell bodies in the SNpc. However, our group reported a decrease in the area of the nigral cell bodies, 30 days after the pontine injury, suggestive of an incipient and ongoing degenerative process [17]. In this condition, we are hypothesizing that the lower nigral gene expression of VMAT2 could induce a decrease in striatal DA release.…”

“…Similarly, pontine injury is associated with compromised nigrostriatal redox homeostasis that can accentuate nigral vulnerability [14,15]. Also at the molecular level, our previous findings demonstrate changes in the gene expression of both transcription factors and genes involved in the phenotype and dopaminergic homeostasis that together suggest an increased risk condition more prone to degeneration [16,17].…”

“…The rats were anesthetized by intraperitoneal (i.p) injection a cocktail of ketamine (mg/ml), diazepan (mg/ ml) and atropine (mg/ml) in a dose of 1 mL/100g and placed in a frame of stereotactic surgery (David Kopf Instruments, Tujunga, CA, USA). Our group has already published the details of the procedure followed in the surgery [17][18][19]. In brief: the neurotoxic lesion of the PPN was performed by means of the injection of an N-methyl-D-aspartate (NMDA) (Sigma, St. Louis, MO, USA) solution in the coordinates (mm) corresponding to the PPN, according to the 20-Paxinos and Watson atlas [20] AP: -7.80 ML: 1.60 DV: -7.60.…”

“…Sample collection: Our group has already published the details of this procedure previously [17,18]. Briefly: the rats were anesthetized by intraperitoneal (i.p) injection a cocktail of ketamine (mg/ml), diazepan (mg/ ml) and atropine (mg/ml) in a dose of 2 mL/100 g. The animals were sacrificed by decapitation.…”