Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Theoretical and Natural Science
Vol. 32, 06 March 2024
Open
Access | Article
Changes in intrinsic excitability of hippocampal pyramidal cells in Parkinson’s disease model
* Author to whom correspondence should be addressed.
Abstract
Parkinson’s disease (PD) is the second most common fatal neurodegenerative disease in the world, and it reduces patients’ quality of life by causing movement disorders (e.g., tremors, muscle stiffness, and impaired balance) and non-motor disorders (e.g., depression, anxiety, and dementia). Previous research has mostly concentrated on dopamine-producing neurons in the substantia nigra compacta (SNc) that are dying off, which restricts therapeutic options and renders the search for disease-modifying therapies fruitless. In order to make a breakthrough, pathological changes in other brain areas deserve more attention. Previous PD studies reported atrophy in the hippocampus, an indispensable part of spatial and temporal memory formation. To answer the question of the cellular mechanism of hippocampus atrophy, this paper intends to research previously uncharted hippocampal intrinsic plasticity alterations. After analysing intercellular recordings of pyramidal neurons gathered from normal mice and genetically engineered PD mice, this paper demonstrates disparities in the intrinsic factors not noted in the previous research, such as peaks and afterhyperpolarization. These findings represent a progressive advancement in our comprehension of hippocampal pyramidal neurons, indicating potential therapeutic targets for Parkinson’s disease treatment via SK channels, BK channels, and sodium channels.
Keywords
Parkinson’s disease, hippocampus, SK channels, BK channels, sodium channels, intrinsic plasticity, pyramidal neurons
References
1. Mamelak M. Parkinson’s Disease, the Dopaminergic Neuron and Gammahydroxybutyrate. Neurol Ther 2018; 7: 5–11.
2. Wirdefeldt K, Adami H-O, Cole P, et al. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 2011; 26: 1–58.
3. Hoffmann A-C, Minakaki G, Menges S, et al. Extracellular aggregated alpha synuclein primarily triggers lysosomal dysfunction in neural cells prevented by trehalose. Sci Rep 2019; 9: 544.
4. Correia Guedes L, Mestre T, Outeiro TF, et al. Are genetic and idiopathic forms of Parkinson’s disease the same disease? Journal of Neurochemistry 2020; 152: 515–522.
5. Nalls MA, Blauwendraat C, Vallerga CL, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. The Lancet Neurology 2019; 18: 1091–1102.
6. Bouchard M, Suchowersky O. Tauopathies: One Disease or Many? Canadian Journal of Neurological Sciences 2011; 38: 547–556.
7. Day JO, Mullin S. The Genetics of Parkinson’s Disease and Implications for Clinical Practice. Genes 2021; 12: 1006.
8. Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA 2020; 323: 548–560.
9. Lane EL. L-DOPA for Parkinson’s disease—a bittersweet pill. European Journal of Neuroscience 2019; 49: 384–398.
10. Costa C, Sgobio C, Siliquini S, et al. Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson’s disease. Brain 2012; 135: 1884–1899.
11. Fahn S, Jankovic J, Hallett M. Medical treatment of Parkinson disease. In: Principles and Practice of Movement Disorders. Elsevier, pp. 119–156.
12. Sawada H, Oeda T, Yamamoto K. Catecholamines and Neurodegeneration in Parkinson’s Disease—From Diagnostic Marker to Aggregations of α-Synuclein. Diagnostics (Basel) 2013; 3: 210–221.
13. Blair JC, Barrett MJ, Patrie J, et al. Brain MRI Reveals Ascending Atrophy in Parkinson’s Disease Across Severity. Frontiers in Neurology; 10, https://www.frontiersin.org/articles/10.3389/ fneur.2019.01329 (2019, accessed 24 July 2023).
14. Pieperhoff P, Südmeyer M, Dinkelbach L, et al. Regional changes of brain structure during progression of idiopathic Parkinson’s disease – A longitudinal study using deformation based morphometry. Cortex 2022; 151: 188–210.
15. Ryan L, Lin C-Y, Ketcham K, et al. The role of medial temporal lobe in retrieving spatial and nonspatial relations from episodic and semantic memory. Hippocampus 2010; 20: 11–18.
16. Scoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 1957; 20: 11–21.
17. Říha P, Brabenec L, Mareček R, et al. The reduction of hippocampal volume in Parkinson’s disease. J Neural Transm (Vienna) 2022; 129: 575–580.
18. Summerfield C, Junqué C, Tolosa E, et al. Structural Brain Changes in Parkinson Disease With Dementia: A Voxel-Based Morphometry Study. Archives of Neurology 2005; 62: 281–285.
19. Helton TD, Otsuka T, Lee M-C, et al. Pruning and loss of excitatory synapses by the parkin ubiquitin ligase. Proceedings of the National Academy of Sciences 2008; 105: 19492–19497.
20. Joelving F c., Billeskov R, Christensen J r., et al. Hippocampal neuron and glial cell numbers in Parkinson’s disease—A stereological study. Hippocampus 2006; 16: 826–833.
21. Korbo L, Amrein I, Lipp H-P, et al. No evidence for loss of hippocampal neurons in non-Alzheimer dementia patients. Acta Neurologica Scandinavica 2004; 109: 132–139.
22. Parra P, Gulyás AI, Miles R. How Many Subtypes of Inhibitory Cells in the Hippocampus? Neuron 1998; 20: 983–993.
23. Spencer RL, Bland ST. Chapter 5 - Hippocampus and Hippocampal Neurons∗. In: Fink G (ed) Stress: Physiology, Biochemistry, and Pathology. Academic Press, pp. 57–68.
24. Sehgal M, Song C, Ehlers VL, et al. Learning to learn - intrinsic plasticity as a metaplasticity mechanism for memory formation. Neurobiol Learn Mem 2013; 105: 186–199.
25. Daou A, Margoliash D. Intrinsic plasticity and birdsong learning. Neurobiology of Learning and Memory 2021; 180: 107407.
26. Pereyra M, Medina JH. AMPA Receptors: A Key Piece in the Puzzle of Memory Retrieval. Front Hum Neurosci 2021; 15: 729051.
27. Graef JD, Godwin DW. Intrinsic plasticity in acquired epilepsy: too much of a good thing? Neuroscientist 2010; 16: 487–495.
28. Kourrich S, Calu DJ, Bonci A. Intrinsic plasticity: an emerging player in addiction. Nat Rev Neurosci 2015; 16: 173–184.
29. Yang Z, Tan Q, Cheng D, et al. The Changes of Intrinsic Excitability of Pyramidal Neurons in Anterior Cingulate Cortex in Neuropathic Pain. Frontiers in Cellular Neuroscience; 12, https://www.frontiersin.org/articles/10.3389/fncel.2018.00436 (2018, accessed 9 July 2023).
30. Tsaur M-L, Sheng M, Lowenstein DH, et al. Differential expression of K+ channel mRNAs in the rat brain and down-regulation in the hippocampus following seizures. Neuron 1992; 8: 1055–1067.
31. Monaghan MM, Menegola M, Vacher H, et al. Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy. Neuroscience 2008; 156: 550–562.
32. Chen X, Yuan L-L, Zhao C, et al. Deletion of Kv4.2 Gene Eliminates Dendritic A-Type K+ Current and Enhances Induction of Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons. J Neurosci 2006; 26: 12143–12151.
33. Ekstrand MI, Galter D. The MitoPark Mouse - an animal model of Parkinson’s disease with impaired respiratory chain function in dopamine neurons. Parkinsonism Relat Disord 2009; 15 Suppl 3: S185-188.
34. Keane PC, Kurzawa M, Blain PG, et al. Mitochondrial Dysfunction in Parkinson’s Disease. Parkinson’s Disease 2011; 2011: e716871.
35. Daou A, Margoliash D. Intrinsic neuronal properties represent song and error in zebra finch vocal learning. Nat Commun 2020; 11: 952.
36. Lu T, Wade K, Hong H, et al. Ion channel mechanisms underlying frequency-firing patterns of the avian nucleus magnocellularis: A computational model. Channels (Austin) 2017; 11: 444–458.
37. Byrne JH. Ionic Mechanisms and Action Potentials (Section 1, Chapter 2) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston, https://nba.uth.tmc.edu/neuroscience/ m/s1/chapter02.html (2023, accessed 1 August 2023).
38. Ahern CA. What activates inactivation? J Gen Physiol 2013; 142: 97–100.
39. Matthews EA, Disterhoft JF. Blocking the BK channel impedes acquisition of trace eyeblink conditioning. Learn Mem 2009; 16: 106–109.
40. Matschke LA, Komadowski MA, Stöhr A, et al. Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson’s disease. Sci Rep 2022; 12: 3180.
41. Ambrosi G, Cerri S, Blandini F. A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. J Neural Transm 2014; 121: 849–859.
42. Verma M, Lizama BN, Chu CT. Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration. Translational Neurodegeneration 2022; 11: 3.
43. Armada-Moreira A, Gomes JI, Pina CC, et al. Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases. Frontiers in Cellular Neuroscience; 14, https://www.frontiersin.org/articles/10.3389/fncel.2020.00090 (2020, accessed 10 November 2023).
44. Bachmann M, Li W, Edwards MJ, et al. Voltage-Gated Potassium Channels as Regulators of Cell Death. Frontiers in Cell and Developmental Biology; 8, https://www.frontiersin.org/articles/ 10.3389/fcell.2020.611853 (2020, accessed 10 November 2023).
45. Serrano-Novillo C, Capera J, Colomer-Molera M, et al. Implication of Voltage-Gated Potassium Channels in Neoplastic Cell Proliferation. Cancers 2019; 11: 287.
46. Du X, Carvalho-de-Souza JL, Wei C, et al. Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia. Proc Natl Acad Sci USA 2020; 117: 6023–6034.
47. Mendonça PR, Vargas-Caballero M, Erdélyi F, et al. Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons. eLife 2016; 5: e16475.
48. Waszkielewicz AM, Gunia A, Szkaradek N, et al. Ion channels as drug targets in central nervous system disorders. Curr Med Chem 2013; 20: 1241–1285.
Data Availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).
- Volume Title
- Proceedings of the 2nd International Conference on Modern Medicine and Global Health
- ISBN (Print)
- 978-1-83558-321-0
- ISBN (Online)
- 978-1-83558-322-7
- Published Date
- 06 March 2024
- Series
- Theoretical and Natural Science
- ISSN (Print)
- 2753-8818
- ISSN (Online)
- 2753-8826
- DOI
- 10.54254/2753-8818/32/20240739
- Copyright
- 06 March 2024
- Open Access
- This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited