LPA signaling is required for dopaminergic neuron development and is reduced through low expression of the LPA1 receptor in a 6-OHDA lesion model of Parkinson’s disease
| Autor: | Feng xiang Sun, Ethan Y. Zhao, Hai lin Han, Xiao yun Yang, Yuchuan Ding, Zhi juan Lin, Xian wei Zeng, Wen xin Zhuang, Hui rong Han, Mei hua Qu, Zhi fang Pan |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Nervous system Tyrosine 3-Monooxygenase Cell Survival Neurogenesis Population Myenteric Plexus Substantia nigra Dermatology Biology Rats Sprague-Dawley chemistry.chemical_compound Parkinsonian Disorders Glial Fibrillary Acidic Protein Lysophosphatidic acid medicine Animals Receptors Lysophosphatidic Acid Oxidopamine education education.field_of_study Tyrosine hydroxylase Glial fibrillary acidic protein Pars compacta Dopaminergic Neurons Mesenchymal Stem Cells General Medicine Substantia Nigra Psychiatry and Mental health medicine.anatomical_structure nervous system chemistry Phosphopyruvate Hydratase biology.protein Female lipids (amino acids peptides and proteins) Neurology (clinical) Neuron Lysophospholipids Neuroscience Central Nervous System Agents Signal Transduction |
| Zdroj: | Neurological Sciences. 36:2027-2033 |
| ISSN: | 1590-3478 1590-1874 |
| DOI: | 10.1007/s10072-015-2295-x |
| Popis: | Lysophosphatidic acid (LPA) is a bioactive phospholipid that activates at least five known G-protein-coupled receptors (GPCRs): LPA1-LPA5. The nervous system is a major locus for LPA1 expression. LPA has been shown to regulate neuronal proliferation, migration, and differentiation during central nervous system development as well as neuronal survival. Furthermore, deficient LPA signaling has been implicated in several neurological disorders including neuropathic pain and schizophrenia. Parkinson's disease (PD) is a neurodegenerative movement disorder that results from the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). The specific molecular pathways that lead to DA neuron degeneration, however, are poorly understood. The influence of LPA in the differentiation of mesenchymal stem cells (MSCs) into DA neurons in vitro and LPA1 expression in a 6-hydroxydopamine (6-OHDA) lesion model of PD in vivo were examined in the present study. LPA induced neuronal differentiation in 80.2 % of the MSC population. These MSCs developed characteristic neuronal morphology and expressed the neuronal marker, neuron-specific enolase (NSE), while expression of the glial marker, glial fibrillary acidic protein (GFAP), was absent. Moreover, 27.6 % of differentiated MSCs were positive for tyrosine hydroxylase (TH), a marker for DA neurons. In the 6-OHDA PD rat model, LPA1 expression in the substantia nigra was significantly reduced compared to control. These results suggest LPA signaling via activation of LPA1 may be necessary for DA neuron development and survival. Furthermore, reduced LPA/LPA1 signaling may be involved in DA neuron degeneration thus contributing to the pathogenesis of PD. |
| Databáze: | OpenAIRE |
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