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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.

Background and Objectives : The knowledge that the cholinergic neurons from pedunculopontine nucleus (PPN) are vulnerable to the degeneration in early stages of the Parkinson disease progression has opened new perspectives to the development of experimental model focused in pontine lesions that could increase the risk of nigral degeneration. In this context it is known that PPN lesioned rats exhibit early changes in the gene expression of proteins responsible for dopaminergic homeostasis. At the same time, it is known that nicotinic cholinergic receptors (nAChRs) mediate the excitatory influence of pontine-nigral projection. However, the effect of PPN injury on the expression of transcription factors that modulate dopaminergic neurotransmission in the adult brain as well as the α7 nAChRs gene expression has not been studied. The main objective of the present work was the study of the effects of the unilateral neurotoxic lesion of PPN in nuclear receptor-related factor 1 (Nurr1), paired-like homeodomain transcription factor 3 (Pitx3), and α7 nAChRs mRNA expression in nigral tissue. Materials and Methods : The molecular biology studies were performed by means of RT-PCR. The following experimental groups were organized: Non-treated rats, N-methyl-D-aspartate (NMDA)-lesioned rats, and Sham operated rats. Experimental subjects were sacrificed 24 h, 48 h and seven days after PPN lesion. Results : Nurr1 mRNA expression, showed a significant increase both 24 h ( p < 0.001) and 48 h ( p < 0.01) after PPN injury. Pitx3 mRNA expression evidenced a significant increase 24 h ( p < 0.001) followed by a significant decrease 48 h and seven days after PPN lesion ( p < 0.01). Finally, the α7 nAChRs nigral mRNA expression remained significantly diminished 24 h, 48 h ( p < 0.001), and 7 days ( p < 0.01) after PPN neurotoxic injury. Conclusion : Taking together these modifications could represent early warning signals and could be the preamble to nigral neurodegeneration events., Competing Interests: The authors declare no conflict of interest.

Background: The degeneration of the pedunculopontine nucleus (PPN) precedes the degeneration of the nigral cells in the pre-symptomatic stages of Parkinson's disease (PD). Although the literature recognizes that a lesion of the PPN increases the vulnerability of dopaminergic cells, it is unknown if this risk is associated with the loss of capability of handling the dopaminergic function., Methods: In this paper, the effects of a unilateral neurotoxic lesion of the PPN in tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) mRNA expression in nigrostriatal tissue were evaluated. Three experimental groups were organized: non-treated rats, NMDA-lesioned rats and Sham-operated rats., Results: Seven days after the PPN lesion, in nigral tissue, TH mRNA expression was higher in comparison with control groups ( p < 0.05); in contrast, VMAT2 mRNA expression showed a significant decrease ( p < 0.01). DAT mRNA expression showed a significant decrease ( p < 0.001) in the striatal tissue. Comparing nigral neuronal density of injured and control rats revealed no significant difference seven days post-PPN injury., Conclusions: Findings suggest that the PPN lesion modifies the mRNA expression of the proteins associated with dopaminergic homeostasis at nigrostriatal level. It could represent vulnerability signals for nigral dopaminergic cells and further increase the risk of degeneration of these cells., Competing Interests: The authors declare no conflict of interest.

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: 0.1M; volume: 0.5µL)] 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 48h after the PPN neurotoxic injury, the GSH concentrations and BDNF expression were significantly increased (p≤0.01). These variables returned to normal values 7days 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., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Introduction: Lesion of the fimbria-fornix causes dysfunction of learning processes and has been used in animal models for the study of Alzheimer's disease., Material and Methods: With the objective of comparing the efficacy of two methods of producing a lesion of the fimbria-fornix, 40 young male Sprague-Dawley rats were distributed in four experimental groups: control (6), falsely lesioned (8), lesion due to aspiration (12) and lesion due to transection (14)., Results: The results showed that whilst with both techniques, in rats, serious cognitive defects were produced, as expressed by the high latencies of escape and small number of crossings of Morris's aquatic labyrinth, the aspiration lesion led to greater mortality than the transection lesion did. Similarly, the aspiration technique in rats induced hyperactivity, aggressiveness and tigmotaxia, while in the rats with lesions due to transection tigmotaxia ceased after their first attempts and hyperactivity on the second day of training., Conclusion: These results would suggest that a bilateral lesion due to transection of the fimbria-fornix is an effective alternative to an aspiration lesion to interrupt this pathway.