AAV-BDNF modulates 5HT2A receptor, glycine receptor subunits, and Nav1.1 channel gene expression in lumbar motoneurons after spinal cord injury
- 1Nencki Institute of Experimental Biology Polish Academy of Sciences, 3 Pasteur Street, Warsaw, 02-093 Poland
- 2Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Life Sciences and Technology, Tongji University, Shanghai, 200065 China
- 3Mossakowski Medical Research Institute, Neurotoxicology Department, Polish Academy of Sciences, 5 Adolfa Pawińskiego Street, Warsaw, 02-106 Poland
Abstract
Background: Proper excitability of spinal motor neurons (MNs) is essential for motor output. Spinal cord injury (SCI) disrupts this network and compromises MN- driven skeletal muscle contractions. We previously showed that tracer-identified MNs innervating ankle extensor and flexor muscles display gene-expression changes toward a more excitatory profile at 2 weeks post-lesion in rats, however, this shift does not restore stepping. Given evidence that brain-derived neurotrophic factor (BDNF) enhances MN excitability and promotes functional recovery, we investigated its effects on gene expression following SCI.
Methods: Adult male rats received retrograde tracers in gastrocnemius lateralis (GL) and tibialis anterior (TA) muscles. Two weeks later, complete low-thoracic transection was followed by bilateral lumbar L1-L2 injection of AAV-BDNF or PBS. Locomotion was assessed on a treadmill and in an open field. BDNF and TrkB transcripts were assessed by RNAscope, while selected receptor, transporter, and ion-channel transcripts were measured in lumbar segments and laser-microdissected GL and TA MNs by RT-qPCR.
Results: At two weeks, AAV-BDNF increased spinal BDNF transcript levels and restored TrkB transcripts in lumbar MNs. It improved treadmill locomotion with plantar placement, alternating step-like movements, and body-weight support, while open-field hindlimb movements were also improved. BDNF selectively increased Htr2a transcripts, particularly in GL MNs, and reduced glycine receptor subunit transcripts. It also reversed SCT-induced Scn1a upregulation in GL and TA MNs. Changes in glutamatergic and GABAA receptor transcripts were selective and MN-population dependent.
Conclusions: These findings show that intraspinal AAV-BDNF is associated with locomotor recovery and transcriptional changes in MN excitability-related genes. The results support a role for BDNF in spinal circuit reactivation after SCT.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11033-026-12984-4.
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BibTeX
@article{ji2026aavbdnf,
title = {{AAV-BDNF modulates 5HT2A receptor, glycine receptor subunits, and Nav1.1 channel gene expression in lumbar motoneurons after spinal cord injury}},
author = {Benjun Ji and Anna Głowacka and Julita Czarkowska-Bauch and Olga Gajewska-Woźniak and Małgorzata Skup},
journal = {Molecular Biology Reports},
year = {2026},
month = nov,
doi = {10.1007/s11033-026-12984-4},
url = {https://doi.org/10.1007/s11033-026-12984-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - AAV-BDNF modulates 5HT2A receptor, glycine receptor subunits, and Nav1.1 channel gene expression in lumbar motoneurons after spinal cord injury
AU - Benjun Ji
AU - Anna Głowacka
AU - Julita Czarkowska-Bauch
AU - Olga Gajewska-Woźniak
AU - Małgorzata Skup
PY - 2026
DA - 2026/11/01
JO - Molecular Biology Reports
DO - 10.1007/s11033-026-12984-4
UR - https://doi.org/10.1007/s11033-026-12984-4
AB - Background: Proper excitability of spinal motor neurons (MNs) is essential for motor output. Spinal cord injury (SCI) disrupts this network and compromises MN- driven skeletal muscle contractions. We previously showed that tracer-identified MNs innervating ankle extensor and flexor muscles display gene-expression changes toward a more excitatory profile at 2 weeks post-lesion in rats, however, this shift does not restore stepping. Given evidence that brain-derived neurotrophic factor (BDNF) enhances MN excitability and promotes functional recovery, we investigated its effects on gene expression following SCI. Methods: Adult male rats received retrograde tracers in gastrocnemius lateralis (GL) and tibialis anterior (TA) muscles. Two weeks later, complete low-thoracic transection was followed by bilateral lumbar L1-L2 injection of AAV-BDNF or PBS. Locomotion was assessed on a treadmill and in an open field. BDNF and TrkB transcripts were assessed by RNAscope, while selected receptor, transporter, and ion-channel transcripts were measured in lumbar segments and laser-microdissected GL and TA MNs by RT-qPCR. Results: At two weeks, AAV-BDNF increased spinal BDNF transcript levels and restored TrkB transcripts in lumbar MNs. It improved treadmill locomotion with plantar placement, alternating step-like movements, and body-weight support, while open-field hindlimb movements were also improved. BDNF selectively increased Htr2a transcripts, particularly in GL MNs, and reduced glycine receptor subunit transcripts. It also reversed SCT-induced Scn1a upregulation in GL and TA MNs. Changes in glutamatergic and GABAA receptor transcripts were selective and MN-population dependent. Conclusions: These findings show that intraspinal AAV-BDNF is associated with locomotor recovery and transcriptional changes in MN excitability-related genes. The results support a role for BDNF in spinal circuit reactivation after SCT. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11033-026-12984-4.
SN - 0301-4851
SN - 1573-4978
ER -