The ratio of excitatory and inhibitory synaptic processes in corticonigral projections: a model of Parkinsons disease with melanin protection
Keywords:
Parkinsons disease, experiment, cortico-nigral projection, melanin, action potential frequency
Abstract
Background. Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the compact part of the substantia nigra. Recent research has also revealed dysfunction in numerous other brain regions, particularly in the motor cortex. Given the lack of a cure for PD, the search for innovative therapeutic strategies remains relevant. Purpose: within the scope of these objectives, the primary aim was to investigate the functional activity of neurons in the compact (SNc) and reticular (SNr) parts of the substantia nigra within a melanin-induced PD model. To achieve this, three series of experiments were conducted on 28 rats, including intact animals, rats with rotenone-induced PD (PD model), and rats with PD receiving melanin. Inhibitory and excitatory effects were recorded during high-frequency stimulation (HFS) of the primary motor cortex (M1). Results: in the PD model, inhibitory effects were completely abolished in SNc neurons, while excitatory effects increased. Following the administration of melanin, both inhibitory and excitatory effects recovered. In the PD model, inhibitory effects in SNr neurons decreased, and the levels of action potential frequency in inhibitory and excitatory effects significantly increased. After melanin administration, inhibitory effects returned to their normal values, and the frequency of action potentials in both types of effects decreased to levels close to normal. Сonclusion: a comparative analysis of the pre- and post-stimulus frequency of activity of SNc and SNr neurons during HFS of the MI in the PD model, in comparison with the norm and under melanin protection conditions, led to the conclusion that neurodegenerative damage is inevitably accompanied by excitotoxicity. This excitotoxicity was successfully mitigated by the protective effect of melanin.
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References
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14. Cacciola A., Milardi D., Quartarone A. Role of cortico-pallidal connectivity in the patho-physiology of dystonia. Brain. 2016;139(9):e48. DOI: 10.1093/brain/aww102
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19. Lucas D.R., Newhouse J.P. The toxic effect of sodium L-glutamate on the inner layers of the retina. Archives of ophthalmology 1957;58(2):193–201. DOI: 10.1001/archopht.1957.00940010205006.
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21. Dong X.X., Wang Y. Qin Z.H. Molecular mechanisms of excitotoxicity and their rele-vance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica. 2009;30(4):379–387. DOI: 10.1038/aps.2009.24
1. Goldman J.G., Sieg E. Cognitive impairment and dementia in Parkinson disease. Clinics in Geriatric Medicine. 2020;36(2):365–77. DOI: 10.1016/j.cger.2020.01.001
2. Uc E.Y., Rizzo M., OShea A.M.J. et al. Longitudinal decline of driving safety in Parkinson disease. Neurology. 2017;89(19):1951–1958. DOI: 10.1212/WNL.0000000000004629
3. Zhou F.M., Lee C.R. Intrinsic and integrative properties of substantia nigra pars reticulata neurons. Neuroscience. 2011;198:69–94. DOI: 10.1016/j.neuroscience.2011.07.061.
4. Guatteo E., Cucchiaroni M.L., Mercuri N.BJ. Substantia nigra control of basal ganglia nuclei. Journal of Neural Transmission. Supplementa. 2009;73: 91–101. DOI: 10.1007/978-3-211-92660-4_7.
5. Carman J.B. Anatomic basis of surgical treatment of Parkinsons disease. The New England Journal of Medicine. 1968;17:919–930. DOI: 10.1056/NEJM196810242791706
6. Weinberger D.R. Implications of the normal brain development for the pathogenesis of schizophrenia. Archives Of General Psychiatry. 1987;44:660–669. DOI: 10.1001/archpsyc.1987.01800190080012.
7. Wise R.A. Roles for nigrostriatal not just mesocorticolimbic-dopamine in reward and addiction. Trends in Neurosciences. 2009;32:517–524. DOI: 10.1016/j.tins.2009.06.004
8. Kolomiets B.P., Deniau J.M., Glowinski J., Thierry A.M. Basal ganglia and processing of cortical information: functional interactions between trans-striatal and trans-subthalamic circuits in the substantia nigra pars reticulata. Neuroscience. 2003;117(4):931–938. DOI: 10.1016/s0306-4522(02)00824-2
9. Menke R.A., Jbabdi S., Miller K.L., Matthews P.M., Zarei M. Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinsons disease. Neuroimage. 2010;52:1175–1180. DOI: 10.1016/j.neuroimage.2010.05.086
10. Kwon H.G., Jang S.H. Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain. Frontiers in Human Neuroscience. 2014.8:41. DOI: 10.3389/fnhum.2014.00041
11. Kornhuber J. The corticonigral projection: reduced glutamate content in the substantia nigra following frontal cortex ablation in the rat. Brain Research.1984;322(1):124–126. DOI: 10.1016/0006-8993(84)91189-2
12. Frankle W.G., Laruelle M., Haber S.N. Stable and unstable activation of the prefrontal cortex with dopaminergic modulation. Neuropsychopharmacology. 2006;31:1627–1636.
13. Sesack S.R, Carr D.B. Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia. Physiology and Behavior. 2002;77:513–517. DOI: 10.1016/s0031-9384(02)00931-9
14. Cacciola A., Milardi D., Quartarone A. Role of cortico-pallidal connectivity in the pathophysiology of dystonia. Brain. 2016;139(9):e48. DOI: 10.1093/brain/aww102
15. Gao X.B. Peptides Electrophysiological effects of MCH on neurons in the hypothalamus. 2009;30(11):2025–2030. DOI: 10.1016/j.peptides.2009.05.006.
16. Paxinos G., Watson C. The rat brain in stereotaxic coordinates. Elsevier, Academic Press. 5th ed. 2005:367.
17. Kilkenny C., Browne W., Cuthill I.C., Emerson M., Altman D.G. Animal research: Reporting in vivo experiments: The ARRIVE guidelines. British Journal of Pharmacology. 2010;160(7):1577–1579. DOI: 10.1111/j.1476-5381.2010.00872.x
18. Matthew R.H., Heather L.S., Peter R.D. Glutamate-mediated excitotoxicity and neuro-degeneration in Alzheimers disease. Comprehensive Cancer Information. 2004;45(5):583–595. DOI: 10.1016/j.neuint.2004.03.007.
19. Lucas D.R., Newhouse J.P. The toxic effect of sodium L-glutamate on the inner layers of the retina. Archives of ophthalmology 1957;58(2):193–201. DOI: 10.1001/archopht.1957.00940010205006.
20. Olney J.W. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science. 1969;164(3880):719–721. DOI: 10.1126/science.164.3880.719.
21. Dong X.X., Wang Y. Qin Z.H. Molecular mechanisms of excitotoxicity and their rele-vance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica. 2009;30(4):379–387. DOI: 10.1038/aps.2009.24
22. Sarkissian J.S., Poghosyan M.V., Danielyan M.A., Stepanyan H.Y., Vardanyan A.V. The assign of depressor synaptic processes in condition of specific neurodegenerative pathology and protection. LAP LAMBERT Academic Publishing RU 2018:252 (in Russ.).
2. Uc E.Y., Rizzo M., O’Shea A.M.J. et al. Longitudinal decline of driving safety in Parkinson disease. Neurology. 2017;89(19):1951–1958. DOI: 10.1212/WNL.0000000000004629
3. Zhou F.M., Lee C.R. Intrinsic and integrative properties of substantia nigra pars reticulata neurons. Neuroscience. 2011;198:69–94. DOI: 10.1016/j.neuroscience.2011.07.061.
4. Guatteo E., Cucchiaroni M.L., Mercuri N.BJ. Substantia nigra control of basal ganglia nu-clei. Journal of Neural Transmission. Supplementa. 2009;73: 91–101. DOI: 10.1007/978-3-211-92660-4_7.
5. Carman J.B. Anatomic basis of surgical treatment of Parkinson's disease. The New England Journal of Medicine. 1968;17:919–930. DOI: 10.1056/NEJM196810242791706
6. Weinberger D.R. Implications of the normal brain development for the pathogenesis of schizophrenia. Archives Of General Psychiatry. 1987;44:660–669. DOI: 10.1001/archpsyc.1987.01800190080012.
7. Wise R.A. Roles for nigrostriatal-not just mesocorticolimbic-dopamine in reward and addic-tion. Trends in Neurosciences. 2009;32:517–524. DOI: 10.1016/j.tins.2009.06.004
8. Kolomiets B.P., Deniau J.M., Glowinski J., Thierry A.M. Basal ganglia and processing of cortical information: functional interactions between trans-striatal and trans-subthalamic circuits in the substantia nigra pars reticulata. Neuroscience. 2003;117(4):931–938. DOI: 10.1016/s0306-4522(02)00824-2
9. Menke R.A., Jbabdi S., Miller K.L., Matthews P.M., Zarei M. Connectivity-based segmenta-tion of the substantia nigra in human and its implications in Parkinsons disease. Neuroimage. 2010;52:1175–1180. DOI: 10.1016/j.neuroimage.2010.05.086
10. Kwon H.G., Jang S.H. Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain. Frontiers in Human Neuroscience. 2014.8:41. DOI: 10.3389/fnhum.2014.00041
11. Kornhuber J. The cortico-nigral projection: reduced glutamate content in the substantia nigra following frontal cortex ablation in the rat. Brain Research.1984;322(1):124–126. DOI: 10.1016/0006-8993(84)91189-2
12. Frankle W.G., Laruelle M., Haber S.N. Stable and unstable activation of the prefrontal cortex with dopaminergic modulation. Neuropsychopharmacology. 2006;31:1627–1636.
13. Sesack S.R, Carr D.B. Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia. Physiology and Behavior. 2002;77:513–517. DOI: 10.1016/s0031-9384(02)00931-9
14. Cacciola A., Milardi D., Quartarone A. Role of cortico-pallidal connectivity in the patho-physiology of dystonia. Brain. 2016;139(9):e48. DOI: 10.1093/brain/aww102
15. Gao X.B. Peptides Electrophysiological effects of MCH on neurons in the hypothalamus. 2009;30(11):2025–2030. DOI: 10.1016/j.peptides.2009.05.006.
16. Paxinos G., Watson C. The rat brain in stereotaxic coordinates. Elsevier, Academic Press. 5th ed. 2005:367.
17. Kilkenny C., Browne W., Cuthill I.C., Emerson M., Altman D.G. Animal research: Report-ing in vivo experiments: The ARRIVE guidelines. British Journal of Pharmacology. 2010;160(7):1577–1579. DOI: 10.1111/j.1476-5381.2010.00872.x
18. Matthew R.H., Heather L.S., Peter R.D. Glutamate-mediated excitotoxicity and neuro-degeneration in Alzheimer’s disease. Comprehensive Cancer Information. 2004;45(5):583–595. DOI: 10.1016/j.neuint.2004.03.007.
19. Lucas D.R., Newhouse J.P. The toxic effect of sodium L-glutamate on the inner layers of the retina. Archives of ophthalmology 1957;58(2):193–201. DOI: 10.1001/archopht.1957.00940010205006.
20. Olney J.W. Brain lesions, obesity, and other disturbances in mice treated with monosodi-um glutamate. Science. 1969;164(3880):719–721. DOI: 10.1126/science.164.3880.719.
21. Dong X.X., Wang Y. Qin Z.H. Molecular mechanisms of excitotoxicity and their rele-vance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica. 2009;30(4):379–387. DOI: 10.1038/aps.2009.24
1. Goldman J.G., Sieg E. Cognitive impairment and dementia in Parkinson disease. Clinics in Geriatric Medicine. 2020;36(2):365–77. DOI: 10.1016/j.cger.2020.01.001
2. Uc E.Y., Rizzo M., OShea A.M.J. et al. Longitudinal decline of driving safety in Parkinson disease. Neurology. 2017;89(19):1951–1958. DOI: 10.1212/WNL.0000000000004629
3. Zhou F.M., Lee C.R. Intrinsic and integrative properties of substantia nigra pars reticulata neurons. Neuroscience. 2011;198:69–94. DOI: 10.1016/j.neuroscience.2011.07.061.
4. Guatteo E., Cucchiaroni M.L., Mercuri N.BJ. Substantia nigra control of basal ganglia nuclei. Journal of Neural Transmission. Supplementa. 2009;73: 91–101. DOI: 10.1007/978-3-211-92660-4_7.
5. Carman J.B. Anatomic basis of surgical treatment of Parkinsons disease. The New England Journal of Medicine. 1968;17:919–930. DOI: 10.1056/NEJM196810242791706
6. Weinberger D.R. Implications of the normal brain development for the pathogenesis of schizophrenia. Archives Of General Psychiatry. 1987;44:660–669. DOI: 10.1001/archpsyc.1987.01800190080012.
7. Wise R.A. Roles for nigrostriatal not just mesocorticolimbic-dopamine in reward and addiction. Trends in Neurosciences. 2009;32:517–524. DOI: 10.1016/j.tins.2009.06.004
8. Kolomiets B.P., Deniau J.M., Glowinski J., Thierry A.M. Basal ganglia and processing of cortical information: functional interactions between trans-striatal and trans-subthalamic circuits in the substantia nigra pars reticulata. Neuroscience. 2003;117(4):931–938. DOI: 10.1016/s0306-4522(02)00824-2
9. Menke R.A., Jbabdi S., Miller K.L., Matthews P.M., Zarei M. Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinsons disease. Neuroimage. 2010;52:1175–1180. DOI: 10.1016/j.neuroimage.2010.05.086
10. Kwon H.G., Jang S.H. Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain. Frontiers in Human Neuroscience. 2014.8:41. DOI: 10.3389/fnhum.2014.00041
11. Kornhuber J. The corticonigral projection: reduced glutamate content in the substantia nigra following frontal cortex ablation in the rat. Brain Research.1984;322(1):124–126. DOI: 10.1016/0006-8993(84)91189-2
12. Frankle W.G., Laruelle M., Haber S.N. Stable and unstable activation of the prefrontal cortex with dopaminergic modulation. Neuropsychopharmacology. 2006;31:1627–1636.
13. Sesack S.R, Carr D.B. Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia. Physiology and Behavior. 2002;77:513–517. DOI: 10.1016/s0031-9384(02)00931-9
14. Cacciola A., Milardi D., Quartarone A. Role of cortico-pallidal connectivity in the pathophysiology of dystonia. Brain. 2016;139(9):e48. DOI: 10.1093/brain/aww102
15. Gao X.B. Peptides Electrophysiological effects of MCH on neurons in the hypothalamus. 2009;30(11):2025–2030. DOI: 10.1016/j.peptides.2009.05.006.
16. Paxinos G., Watson C. The rat brain in stereotaxic coordinates. Elsevier, Academic Press. 5th ed. 2005:367.
17. Kilkenny C., Browne W., Cuthill I.C., Emerson M., Altman D.G. Animal research: Reporting in vivo experiments: The ARRIVE guidelines. British Journal of Pharmacology. 2010;160(7):1577–1579. DOI: 10.1111/j.1476-5381.2010.00872.x
18. Matthew R.H., Heather L.S., Peter R.D. Glutamate-mediated excitotoxicity and neuro-degeneration in Alzheimers disease. Comprehensive Cancer Information. 2004;45(5):583–595. DOI: 10.1016/j.neuint.2004.03.007.
19. Lucas D.R., Newhouse J.P. The toxic effect of sodium L-glutamate on the inner layers of the retina. Archives of ophthalmology 1957;58(2):193–201. DOI: 10.1001/archopht.1957.00940010205006.
20. Olney J.W. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science. 1969;164(3880):719–721. DOI: 10.1126/science.164.3880.719.
21. Dong X.X., Wang Y. Qin Z.H. Molecular mechanisms of excitotoxicity and their rele-vance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica. 2009;30(4):379–387. DOI: 10.1038/aps.2009.24
22. Sarkissian J.S., Poghosyan M.V., Danielyan M.A., Stepanyan H.Y., Vardanyan A.V. The assign of depressor synaptic processes in condition of specific neurodegenerative pathology and protection. LAP LAMBERT Academic Publishing RU 2018:252 (in Russ.).
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Published
2024-04-01
How to Cite
Pogosyan, M., Sarkisyan, R., Andriasyan, A., Khachatryan, L., Avetisyan, S., Minasyan, A., Stepanyan, A., Sarkisyan, V., Manukyan, A., & Sarkisyan, D. (2024). The ratio of excitatory and inhibitory synaptic processes in corticonigral projections: a model of Parkinsons disease with melanin protection. Psychology. Psychophysiology, 17(1), 103-118. https://doi.org/10.14529/jpps240110
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Psychophysiology
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