The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS
Само за регистроване кориснике
2020
Аутори
Jara, Javier H.Sheets, Patrick L.
Nigro, Maximiliano Jose
Perić, Mina
Brooks, Carolyn
Heller, Daniel B.
Martina, Marco
Andjus, Pavle R.
Ozdinler, P. Hande
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1(G93A) mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from ...hSOD1(G93A) and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies.
Кључне речи:
upper motor neurons / primary lateral sclerosis / neuronal vulnerability / microcircuit / hereditary spastic paraplegia / corticospinal motor neurons / amyotrophic lateral sclerosisИзвор:
Frontiers in Molecular Neuroscience, 2020, 13Издавач:
- Frontiers Media Sa, Lausanne
Финансирање / пројекти:
- NIA [RO1AG061708]
- Les Turner ALS Foundation
- National Institutes of Health (NIH) [NS066675]
- Amyotrophic Lateral Sclerosis Association (ALSA) Milton Safenowitz Postdoctoral Fellowship
- AUTOIGG - Automated functional screening of IGGS for diagnostics of neurodegenerative diseases (EU-H2020-778405)
DOI: 10.3389/fnmol.2020.00073
ISSN: 1662-5099
WoS: 000538874900001
Scopus: 2-s2.0-85085882700
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Jara, Javier H. AU - Sheets, Patrick L. AU - Nigro, Maximiliano Jose AU - Perić, Mina AU - Brooks, Carolyn AU - Heller, Daniel B. AU - Martina, Marco AU - Andjus, Pavle R. AU - Ozdinler, P. Hande PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1327 AB - The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1(G93A) mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1(G93A) and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies. PB - Frontiers Media Sa, Lausanne T2 - Frontiers in Molecular Neuroscience T1 - The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS VL - 13 DO - 10.3389/fnmol.2020.00073 ER -
@article{ author = "Jara, Javier H. and Sheets, Patrick L. and Nigro, Maximiliano Jose and Perić, Mina and Brooks, Carolyn and Heller, Daniel B. and Martina, Marco and Andjus, Pavle R. and Ozdinler, P. Hande", year = "2020", abstract = "The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1(G93A) mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1(G93A) and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies.", publisher = "Frontiers Media Sa, Lausanne", journal = "Frontiers in Molecular Neuroscience", title = "The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS", volume = "13", doi = "10.3389/fnmol.2020.00073" }
Jara, J. H., Sheets, P. L., Nigro, M. J., Perić, M., Brooks, C., Heller, D. B., Martina, M., Andjus, P. R.,& Ozdinler, P. H.. (2020). The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS. in Frontiers in Molecular Neuroscience Frontiers Media Sa, Lausanne., 13. https://doi.org/10.3389/fnmol.2020.00073
Jara JH, Sheets PL, Nigro MJ, Perić M, Brooks C, Heller DB, Martina M, Andjus PR, Ozdinler PH. The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS. in Frontiers in Molecular Neuroscience. 2020;13. doi:10.3389/fnmol.2020.00073 .
Jara, Javier H., Sheets, Patrick L., Nigro, Maximiliano Jose, Perić, Mina, Brooks, Carolyn, Heller, Daniel B., Martina, Marco, Andjus, Pavle R., Ozdinler, P. Hande, "The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS" in Frontiers in Molecular Neuroscience, 13 (2020), https://doi.org/10.3389/fnmol.2020.00073 . .