Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS
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Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS. / Montañana-Rosell, Roser; Selvan, Raghavendra; Hernández-Varas, Pablo; Kaminski, Jan M.; Sidhu, Simrandeep Kaur; Ahlmark, Dana B.; Kiehn, Ole; Allodi, Ilary.
I: Science Advances, Bind 10, Nr. 22, eadk3229, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS
AU - Montañana-Rosell, Roser
AU - Selvan, Raghavendra
AU - Hernández-Varas, Pablo
AU - Kaminski, Jan M.
AU - Sidhu, Simrandeep Kaur
AU - Ahlmark, Dana B.
AU - Kiehn, Ole
AU - Allodi, Ilary
PY - 2024
Y1 - 2024
N2 - Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons. A major focus has been directed to motor neuron intrinsic properties as a cause for degeneration, while less attention has been given to the contribution of spinal interneurons. In the present work, we applied multiplexing detection of transcripts and machine learning-based image analysis to investigate the fate of multiple spinal interneuron populations during ALS progression in the SOD1G93A mouse model. The analysis showed that spinal inhibitory interneurons are affected early in the disease, before motor neuron death, and are characterized by a slow progressive degeneration, while excitatory interneurons are affected later with a steep progression. Moreover, we report differential vulnerability within inhibitory and excitatory subpopulations. Our study reveals a strong interneuron involvement in ALS development with interneuron specific degeneration. These observations point to differential involvement of diverse spinal neuronal circuits that eventually may be determining motor neuron degeneration.
AB - Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons. A major focus has been directed to motor neuron intrinsic properties as a cause for degeneration, while less attention has been given to the contribution of spinal interneurons. In the present work, we applied multiplexing detection of transcripts and machine learning-based image analysis to investigate the fate of multiple spinal interneuron populations during ALS progression in the SOD1G93A mouse model. The analysis showed that spinal inhibitory interneurons are affected early in the disease, before motor neuron death, and are characterized by a slow progressive degeneration, while excitatory interneurons are affected later with a steep progression. Moreover, we report differential vulnerability within inhibitory and excitatory subpopulations. Our study reveals a strong interneuron involvement in ALS development with interneuron specific degeneration. These observations point to differential involvement of diverse spinal neuronal circuits that eventually may be determining motor neuron degeneration.
U2 - 10.1126/sciadv.adk3229
DO - 10.1126/sciadv.adk3229
M3 - Journal article
C2 - 38820149
AN - SCOPUS:85195006498
VL - 10
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 22
M1 - eadk3229
ER -
ID: 394526525