Regulation of Parvalbumin Interactome in the Perilesional Cortex after Experimental Traumatic Brain Injury
| Autor: | Noora Puhakka, Asla Pitkänen, Johanna Hiltunen, Anssi Lipponen, Günther Sperk, Xavier Ekolle Ndode-Ekane, Meinrad Drexel |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Pathology medicine.medical_specialty Traumatic brain injury Inhibitory postsynaptic potential gamma-Aminobutyric acid Rats Sprague-Dawley Interneurons Postsynaptic potential Cortex (anatomy) Brain Injuries Traumatic medicine Animals GABRD Epilepsy biology General Neuroscience medicine.disease Rats Parvalbumins medicine.anatomical_structure nervous system biology.protein GABAergic Parvalbumin medicine.drug |
| Zdroj: | Neuroscience. 475:52-72 |
| ISSN: | 0306-4522 |
| Popis: | Traumatic brain injury (TBI) causes 10–20% of structural epilepsy, with seizures typically originating in the cortex. Alterations in the neuronal microcircuits in the cortical epileptogenic zone, however, are poorly understood. Here, we assessed TBI-induced changes in perisomatic gamma aminobutyric acid (GABA)-ergic innervation in the perilesional cortex. We hypothesized that TBI will damage parvalbumin (PV)-immunoreactive inhibitory neurons and induce regulation of the associated GABAergic molecular interactome. TBI was induced in adult male Sprague-Dawley rats by lateral fluid-percussion injury. At 1-month post-TBI, the number of PV-positive somata was plotted on unfolded cortical maps and the distribution and density of immunopositive terminals analyzed. Qualitative analysis revealed either patchy microlesions of several hundred micrometers in diameter or diffuse neuronal loss. Quantitative analysis demonstrated a reduction in the number of PV-positive interneurons in patches down to 0% of that in sham-operated controls in the perilesional cortex. In the majority of patches, the cell numbers ranged from 71% to 90% that of the controls. The loss of PV-positive somata was accompanied by decreased axonal labeling. In situ hybridization revealed downregulated PV mRNA expression in the perilesional cortex. Gene Set Enrichment Analysis indicated a robustly downregulated expression profile of PV-related genes, which was confirmed by quantitative reverse transcriptase polymerase chain reaction. Specifically, we found that genes encoding postsynaptic GABA-A receptor genes, Gabrg2 and Gabrd, were downregulated in TBI animals compared with controls. Our data suggests that patchy reduction in PV-positive perisomatic inhibitory innervation contributes to the development of focal cortical inhibitory deficit after TBI. |
| Databáze: | OpenAIRE |
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