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Stålhandske, Lada
Publications (3 of 3) Show all publications
Kononenko, O., Watanabe, H., Stålhandske, L., Zarelius, A., Clausen, F., Yakovleva, T., . . . Marklund, N. (2019). Focal traumatic brain injury induces neuroplastic molecular responses in lumbar spinal cord. Restorative Neurology and Neuroscience, 37(2), 87-96
Open this publication in new window or tab >>Focal traumatic brain injury induces neuroplastic molecular responses in lumbar spinal cord
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2019 (English)In: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 37, no 2, p. 87-96Article in journal (Refereed) Published
Abstract [en]

Background/Objectives: Motor impairment induced by traumatic brain injury (TBI) may be mediated through changes in spinal molecular systems regulating neuronal plasticity. We assessed whether a focal controlled cortical impact (CCI) TBI in the rat alters expression of the Tgfb1, c-Fos, Bdnf and Gap43 neuroplasticity genes in lumbar spinal cord.

Approach/Methods: Adult male Sprague-Dawley rats (n = 8) were subjected to a right-side CCI over the anterior sensorimotor hindlimb representation area or sham-injury (n=8). Absolute expression levels of Tgfb1, c-Fos, Bdnf, and Gapd43 genes were measured by droplet digital PCR in ipsi- and contralesional, dorsal and ventral quadrants of the L4 and L5 spinal cord. The neuronal activity marker c-Fos was analysed by immunohistochemistry in the dorsal L4 and L5 segments. The contra- vs. ipsilesional expression pattern was examined as the asymmetry index, AI.

Results: The Tgfb1 mRNA levels were significantly higher in the CCI vs. sham-injured rats, and in the contra- vs. ipsilesional dorsal domains in the CCI group. The number of c-Fos-positive cells was elevated in the L4 and L5 segments; and on the contralesional compared to the ipsilesional side in the CCI group. The c-Fos AI in the dorsal laminae was significantly increased by CCI.

Conclusions: The results support the hypothesis that focal TBI induces plastic alterations in the lumbar spinal cord that may contribute to either motor recovery or maladaptive motor responses.

Place, publisher, year, edition, pages
IOS PRESS, 2019
Keywords
Traumatic brain injury, Tgfb1, c-Fos, spinal cord, plasticity
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:uu:diva-383037 (URN)10.3233/RNN-180882 (DOI)000464944000001 ()30856132 (PubMedID)
Funder
Swedish Research CouncilSwedish Institute
Note

De tre första författarna delar förstaförfattarskapet.

de två sista författarna delar sistaförfattarskapet.

Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-05-08Bibliographically approved
Bazov, I., Sarkisyan, D., Kononenko, O., Watanabe, H., Taqi, M. M., Stålhandske, L., . . . Bakalkin, G. (2018). Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain. Cerebral Cortex, 28(9), 3129-3142
Open this publication in new window or tab >>Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain
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2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 9, p. 3129-3142Article in journal (Refereed) Published
Abstract [en]

Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF). USF2 activates PDYN transcription in model systems, and binds to nonmethylated CGI in dlPFC. USF2 and PDYN expression is correlated, and USF2 and PDYN proteins are co-localized in dlPFC. Segregation of activatory TF and repressive CGI methylation may ensure contrasting PDYN expression in neurons and glia in human brain.

Keywords
DNA methylation, cell type-specific expression, human brain, neuropeptides, transcription
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-343193 (URN)10.1093/cercor/bhx181 (DOI)000443545600005 ()28968778 (PubMedID)
Funder
Swedish Research Council, K2014-62X-12190-19-5Forte, Swedish Research Council for Health, Working Life and Welfare, 2009-1709Forte, Swedish Research Council for Health, Working Life and Welfare, 259-2012-23NIH (National Institute of Health), P30 GM103328
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2020-02-17Bibliographically approved
Bakalkin, G., Watanabe, H., Kononenko, O., Stålhandske, L. & Marklund, N. (2016). TBI induced spinal cord plasticity: The endogenous opioid system mediates trauma effects on motor reflexes. Brain Injury, 30(5-6), 712-712
Open this publication in new window or tab >>TBI induced spinal cord plasticity: The endogenous opioid system mediates trauma effects on motor reflexes
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2016 (English)In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 30, no 5-6, p. 712-712Article in journal, Meeting abstract (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-299658 (URN)000376388200514 ()
Available from: 2016-07-25 Created: 2016-07-25 Last updated: 2017-11-28Bibliographically approved
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