Impacts of epidural electrical stimulation on Wnt signaling,FAAH, and BDNF following thoracic spinal cord injury in rat |
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Authors: | Meysam Ghorbani Parviz Shahabi Pouran Karimi Hamid Soltani-Zangbar Mohammad Morshedi Soheila Bani Mohsen Jafarzadehgharehziaaddin Behnaz Sadeghzadeh-Oskouei Ali Ahmadalipour |
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Affiliation: | 1. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran;2. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;3. Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran |
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Abstract: | Electrical stimulation (ES) has been shown to improve some of impairments after spinal cord injury (SCI), but the underlying mechanisms remain unclear. The Wnt signaling pathways and the endocannabinoid system appear to be modulated in response to SCI. This study aimed to investigate the effect of ES therapy on the activity of canonical/noncanonical Wnt signaling pathways, brain-derived neurotrophic factor (BDNF), and fatty-acid amide hydrolase (FAAH), which regulate endocannabinoids levels. Forty male Wistar rats were randomly divided into four groups: (a) Sham, (b) laminectomy + epidural subthreshold ES, (c) SCI, and (d) SCI + epidural subthreshold ES. A moderate contusion SCI was performed at the thoracic level (T10). Epidural subthreshold ES was delivered to upper the level of T10 segment every day (1 hr/rat) for 2 weeks. Then, animals were killed and immunoblotting was used to assess spinal cord parameters. Results revealed that ES intervention for 14 days could significantly increase wingless-type3 (Wnt3), Wnt7, β-catenin, Nestin, and cyclin D1 levels, as well as phosphorylation of glycogen synthase kinase 3β and Jun N-terminal kinase. Additionally, SCI reduced BDNF and FAAH levels, and ES increased BDNF and FAAH levels in the injury site. We propose that ES therapy may improve some of impairments after SCI through Wnt signaling pathways. Outcomes also suggest that BDNF and FAAH are important players in the beneficial impacts of ES therapy. However, the precise mechanism of BDNF, FAAH, and Wnt signaling pathways on SCI requires further investigation. |
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Keywords: | epidural subthreshold electrical stimulation FAAH spinal cord injury Wnt signaling |
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