Journal Article

DZNE-2026-00456

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spinal motoneuron excitability is homeostatically regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice.

Antonucci, S. ; Caron, G. ; Dikwella, N. ; Krishnamurthy, S. S. ; Harster, A. ; Wasicki, B. ; Zarrin, H. ; Tahanis, A. ; Heuvel, F. O. ; Danner, S. M. ; Ludolph, A. C.DZNE* ; Grycz, K. ; Bączyk, M. ; Zytnicki, D. ; Roselli, F. (Last author)DZNE*

2026
Elsevier Jena

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Please use a persistent id in citations: doi:10.1016/j.pneurobio.2026.102905

Abstract: Homeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in the context of Amyotrophic Lateral Sclerosis (ALS), an excessive gain in feedback loops might hyper- or hypo-excite motoneurons (MNs) and contribute to the pathogenesis. Here, we investigated how the neuromodulation of MN intrinsic properties is homeostatically controlled in presymptomatic adult SOD1(G93A) mice and in the age-matched control WT mice. First, we determined that Adrb2 and Adrb3 adrenergic receptors, which are Gs-coupled receptors and subject to tight and robust feedback loops, are specifically expressed in spinal MNs of both SOD1 and WT mice at P45. We then demonstrated that these receptors elicit a so-far overlooked neuromodulation of the electrical properties of MNs, in particular the frequency-current gain, a crucial determinant of excitability. These electrical properties are homeostatically regulated following receptor engagement, which triggers ion channel transcriptional changes and downregulates those receptors. These homeostatic feedbacks are not dysregulated in presymptomatic SOD1 mice, and they set the MN excitability upon β-adrenergic neuromodulation.

Keyword(s): Animals (MeSH) ; Motor Neurons: physiology (MeSH) ; Motor Neurons: metabolism (MeSH) ; Motor Neurons: drug effects (MeSH) ; Mice, Transgenic (MeSH) ; Spinal Cord: cytology (MeSH) ; Spinal Cord: metabolism (MeSH) ; Mice (MeSH) ; Superoxide Dismutase-1: genetics (MeSH) ; Homeostasis: physiology (MeSH) ; Amyotrophic Lateral Sclerosis: metabolism (MeSH) ; Amyotrophic Lateral Sclerosis: physiopathology (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Receptors, Adrenergic, beta-3: metabolism (MeSH) ; Disease Models, Animal (MeSH) ; Receptors, Adrenergic, beta-2: metabolism (MeSH) ; Superoxide Dismutase: genetics (MeSH) ; Amyotrophic Lateral Sclerosis ; Channelome ; G protein-coupled receptors ; Homeostatic regulation ; Transcriptomics ; in vivo intracellular electrophysiology ; β-adrenergic neuromodulation ; Superoxide Dismutase-1 ; Receptors, Adrenergic, beta-3 ; Receptors, Adrenergic, beta-2 ; Superoxide Dismutase ; Sod1 protein, mouse

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Contributing Institute(s):

1. Metabolic Changes in Neurodegeneration (AG Roselli)
2. Clinical Study Center (Ulm) (Clinical Study Center (Ulm))

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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