Lentiviral delivery of human erythropoietin attenuates hippocampal atrophy and improves cognition in the R6/2 mouse model of Huntington's disease
| Autor: | Josef Priller, Simone Rolfes, Ekaterini-Maria Lyras, Koliane Ouk, David A. D. Munro, Eduardo Matute, Christoph Harms, Chotima Böttcher |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
physiopathology [Huntington Disease] Hippocampus Mice 0302 clinical medicine Cognition Neural Stem Cells Medicine Transgenic mice Gene delivery Neurogenesis Neurodegeneration Huntington's disease Organ Size Huntington Disease Neurology pathology [Huntington Disease] Intracerebroventricular Female EPO protein human medicine.drug Spatial Navigation Genetically modified mouse medicine.medical_specialty genetics [Erythropoietin] Mice Transgenic Transfection Neuroprotection metabolism [Erythropoietin] lcsh:RC321-571 03 medical and health sciences Atrophy Internal medicine ddc:570 Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Erythropoietin Injections Intraventricular business.industry Lentivirus Genetic Therapy medicine.disease Disease Models Animal 030104 developmental biology Endocrinology pathology [Hippocampus] Therapy business Trinucleotide repeat expansion 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of disease 144, 105024 (2020). doi:10.1016/j.nbd.2020.105024 Neurobiology of Disease, Vol 144, Iss, Pp 105024-(2020) Rolfes, S, Munro, D, Lyras, E-M, Matute, E, Ouk, K, Harms, C, Böttcher, C & Priller, J 2020, ' Lentiviral delivery of human erythropoietin attenuates hippocampal atrophy and improves cognition in the R6/2 mouse model of Huntington's disease ', Neurobiology of disease . https://doi.org/10.1016/j.nbd.2020.105024 |
| DOI: | 10.1016/j.nbd.2020.105024 |
| Popis: | Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a trinucleotide (CAG) repeat expansion in the huntingtin gene (HTT). The R6/2 transgenic mouse model of HD expresses exon 1 of the human HTT gene with approximately 150 CAG repeats. R6/2 mice develop progressive behavioural abnormalities, impaired neurogenesis, and atrophy of several brain regions. In recent years, erythropoietin (EPO) has been shown to confer neuroprotection and enhance neurogenesis, rendering it a promising molecule to attenuate HD symptoms. In this study, the therapeutic potential of EPO was evaluated in female R6/2 transgenic mice. A single bilateral injection of a lentivirus encoding human EPO (LV-hEPO) was performed into the lateral ventricles of R6/2 mice at disease onset (8 weeks of age). Control groups were either untreated or injected with a lentivirus encoding green fluorescent protein (LV-GFP). Thirty days after virus administration, hEPO mRNA and protein were present in injected R6/2 brains. Compared to control R6/2 mice, LV-hEPO-treated R6/2 mice exhibited reduced hippocampal atrophy, increased neuroblast branching towards the dentate granular cell layer, and improved spatial cognition. Our results suggest that LV-hEPO administration may be a promising strategy to reduce cognitive impairment in HD. |
| Databáze: | OpenAIRE |
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