Semaphorin 7A restricts serotonergic innervation and ensures recovery after spinal cord injury.

Loy, Kristina; Fourneau, Julie; Meng, Ning; Denecke, Carmen; Locatelli, Giuseppe; Bareyre, Florence M (2021). Semaphorin 7A restricts serotonergic innervation and ensures recovery after spinal cord injury. Cellular and molecular life sciences : CMLS, 78(6), pp. 2911-2927. Springer 10.1007/s00018-020-03682-w

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Descending serotonergic (5-HT) projections originating from the raphe nuclei form an important input to the spinal cord that control basic locomotion. The molecular signals that control this projection pattern are currently unknown. Here, we identify Semaphorin7A (Sema7A) as a critical cue that restricts serotonergic innervation in the spinal cord. Sema7A deficient mice show a marked increase in serotonergic fiber density in all layers of the spinal cord while the density of neurons expressing the corresponding 5-HTR2α receptor remains unchanged. These alterations appear to be successfully compensated as no obvious changes in rhythmic locomotion and skilled stepping are observed in adult mice. When the system is challenged with a spinal lesion, serotonergic innervation patterns in both Sema7A-deficient and -competent mice evolve over time with excessive innervation becoming most pronounced in the dorsal horn of Sema7A-deficient mice. These altered serotonergic innervation patterns correlate with diminished functional recovery that predominantly affects rhythmic locomotion. Our findings identify Sema7A as a critical regulator of serotonergic circuit formation in the injured spinal cord.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Locatelli, Giuseppe

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1420-9071

Publisher:

Springer

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

25 Jan 2021 12:11

Last Modified:

05 Dec 2022 15:44

Publisher DOI:

10.1007/s00018-020-03682-w

PubMed ID:

33128105

Uncontrolled Keywords:

Locomotion Patterning Recovery Semaphorin7A Serotonin Spinal cord injury

BORIS DOI:

10.48350/150916

URI:

https://boris.unibe.ch/id/eprint/150916

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