Nurr1, Pitx3, and α7 nAChRs mRNA Expression in Nigral Tissue of Rats with Pedunculopontine Neurotoxic Lesion
Open Access
- 20 September 2019
- Vol. 55 (10), 616
- https://doi.org/10.3390/medicina55100616
Abstract
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.Keywords
This publication has 63 references indexed in Scilit:
- Specific needs of dopamine neurons for stimulation in order to survive: implication for Parkinson diseaseThe FASEB Journal, 2013
- Nuclear Import and Export Signals Control the Subcellular Localization of Nurr1 Protein in Response to Oxidative Stress*Online Journal of Public Health Informatics, 2013
- Altered transcription factor trafficking in oxidatively-stressed neuronal cellsBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2012
- α7 Nicotinic ACh Receptors as a Ligand-Gated Source of Ca2+ Ions: The Search for a Ca2+ OptimumAdvances in Experimental Medicine and Biology, 2012
- Reactive oxygen species inactivate neuronal nicotinic acetylcholine receptors through a highly conserved cysteine near the intracellular mouth of the channel: implications for diseases that involve oxidative stressJournal Of Physiology-London, 2011
- Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and NeurotoxicityPharmaceuticals, 2011
- Quantitative mapping of T1 and T2* discloses nigral and brainstem pathology in early Parkinson's diseaseNeuroImage, 2010
- Multiple roles for nicotine in Parkinson's diseaseBiochemical Pharmacology, 2009
- Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmissionBritish Journal of Pharmacology, 2008
- The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neuronsMolecular and Cellular Neuroscience, 2005