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5 results on '"HD transgenic mice"'

1. Characterization of somatostatin receptors and associated signaling pathways in pancreas of R6/2 transgenic mice.

Author

Somvanshi, Rishi K., Jhajj, Amrit, Heer, Michael, and Kumar, Ujendra

Subjects
*SOMATOSTATIN receptors, *CELL communication, *GLUCAGON, *TYROSINE hydroxylase, *TRANSGENIC mice
Abstract

The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (β), glucagon (α) and somatostatin (δ) producing cells in the pancreatic islets of 11 weeks old R6/2 Huntington's Disease transgenic (HD tg ) and age-matched wild type ( wt ) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptophysin (SYP) in addition to signal transduction pathways associated with diabetes. In R6/2 mice, islets are relatively smaller in size, exhibit enhanced expression and nuclear inclusion of m Htt along with the loss of insulin, glucagon and somatostatin expression. In comparison to wt , R6/2 mice display enhanced mRNA for all SSTRs except SSTR2. In the pancreatic lysate, SSTR1, 4 and 5 immunoreactivity decreases whereas SSTR3 immunoreactivity increases with no discernible changes in SSTR2 immunoreactivity. Furthermore, at the cellular level, R6/2 mice exhibit a receptor specific distributional pattern of SSTRs like immunoreactivity and colocalization with β, α and δ cells. While GAD expression is increased, TH and SYP immunoreactivity was decreased in R6/2 mice, anticipating a cross-talk between the CNS and pancreas in diabetes pathophysiology. We also dissected out the changes in signaling pathway and found decreased activation and expression of PKA, AKT, ERK1/2 and STAT3 in R6/2 mice pancreas. These findings suggest that the impaired organization of SSTRs within islets may lead to perturbed hormonal regulation and signaling. These interconnected complex events might shed new light on the pathogenesis of diabetes in neurodegenerative diseases and the role of SSTRs in potential therapeutic intervention. [ABSTRACT FROM AUTHOR]

Published
2018
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2. Long-term lentiviral-mediated expression of ciliary neurotrophic factor in the striatum of Huntington's disease transgenic mice

Author

Zala, Diana, Bensadoun, Jean-Charles, Pereira de Almeida, Luis, Leavitt, Blair R., Gutekunst, Claire-Anne, Aebischer, Patrick, Hayden, Michael R., and Déglon, Nicole

Subjects
*NEUROTROPHINS, *NEUROTOXICOLOGY, *HUNTINGTON disease, *GENE expression
Abstract

Ciliary neurotrophic factor (CNTF) has been shown to prevent behavioral deficits and striatal degeneration in neurotoxic models of Huntington''s disease (HD), but its effect in a genetic model has not been evaluated. Lentiviral vectors expressing the human CNTF or LacZ reporter gene were therefore injected in the striatum of wild-type (WT) and transgenic mice expressing full-length huntingtin with 72 CAG repeats (YAC72). Behavioral analysis showed increased locomotor activity in 5- to 6-month-old YAC72-LacZ mice compared to WT-LacZ animals. Interestingly, CNTF expression reduced the activity levels of YAC72 mice compared to control animals. In both WT and YAC72 mice, CNTF expression was demonstrated in striatal punches, up to a year after lentiviral injection. Stereological analysis revealed that the number of LacZ and DARPP-32-positive neurons were decreased in YAC72-LacZ mice compared to WT-LacZ animals. Assessment of the benefit of CNTF expression in the YAC72 mice was, however, complicated by a down-regulation of DARPP-32 and to a lesser extent of NeuN in all mice treated with CNTF. The expression of the neuronal marker NADPH-d was unaffected by CNTF, but expression of the astrocytic marker glial fibrillary acidic protein (GFAP) was increased. Finally, a reduction of the number of striatal dark cells was observed in YAC mice treated with CNTF compared to LacZ. These data indicate that sustained striatal expression of CNTF can be achieved with lentiviruses. Further studies are, however, needed to investigate the intracellular signaling pathways mediating the long-term effects of CNTF expression on dopamine signaling, glial cell activation and how these changes may affect HD pathology. [Copyright &y& Elsevier]

Published
2004
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3. Cell-Type-Specific Gene Expression Profiling in Adult Mouse Brain Reveals Normal and Disease-State Signatures

Author

Merienne, Nicolas, Meunier, Cécile, Schneider, Anne, Seguin, Jonathan, Nair, Satish, Rocher, Anne, Le Gras, Stéphanie, Keime, Celine, Faull, Richard, Pellerin, Luc, Chatton, Jean-Yves, Neri, Christian, Mérienne, Karine, Déglon, Nicole, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Lausanne (UNIL), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), University of Auckland [Auckland], Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Département d'Informatique et de Recherche Opérationnelle [Montreal] (DIRO), Université de Montréal (UdeM), Reproduction et développement des plantes (RDP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon, Biologie et Pathologie du Neurone (Brain-C), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Montréal [Montréal], École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, [SDV]Life Sciences [q-bio], striatum, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, HD patients, Mice, Transgenic, Laser Capture Microdissection, Epigenesis, Genetic, Mice, transcriptomics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, RNA, Messenger, epigenetics, HD transgenic mice, Brain/metabolism, DNA/chemistry, Gene Expression Profiling/methods, Huntington Disease/genetics, Huntington Disease/metabolism, Laser Capture Microdissection/methods, MicroRNAs/metabolism, Nucleic Acid Conformation, RNA, Messenger/metabolism, Transcription Factors/metabolism, Huntington’s disease, cell-type-specific profiling, Gene Expression Profiling, Brain, DNA, MicroRNAs, Huntington Disease, Transcription Factors
Abstract

International audience; The role of brain cell-type-specific functions and profiles in pathological and non-pathological contexts is still poorly defined. Such cell-type-specific gene expression profiles in solid, adult tissues would benefit from approaches that avoid cellular stress during isolation. Here, we developed such an approach and identified highly selective transcriptomic signatures in adult mouse striatal direct and indirect spiny projection neurons, astrocytes, and microglia. Integrating transcriptomic and epigenetic data, we obtained a comprehensive model for cell-type-specific regulation of gene expression in the mouse striatum. A cross-analysis with transcriptomic and epigenomic data generated from mouse and human Huntington’s disease (HD) brains shows that opposite epigenetic mechanisms govern the transcriptional regulation of striatal neurons and glial cells and may contribute to pathogenic and compensatory mechanisms. Overall, these data validate this less stressful method for the investigation of cellular specificity in the adult mouse brain and demonstrate the potential of integrative studies using multiple databases.

Published
2019
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4. Cell-Type-Specific Gene Expression Profiling in Adult Mouse Brain Reveals Normal and Disease-State Signatures.

Author

Merienne N, Meunier C, Schneider A, Seguin J, Nair SS, Rocher AB, Le Gras S, Keime C, Faull R, Pellerin L, Chatton JY, Neri C, Merienne K, and Déglon N

Subjects
Animals, DNA chemistry, Epigenesis, Genetic, Gene Expression Profiling methods, Humans, Huntington Disease metabolism, Laser Capture Microdissection methods, Male, Mice, Mice, Transgenic, MicroRNAs metabolism, Nucleic Acid Conformation, RNA, Messenger metabolism, Transcription Factors metabolism, Brain metabolism, Huntington Disease genetics
Abstract

The role of brain cell-type-specific functions and profiles in pathological and non-pathological contexts is still poorly defined. Such cell-type-specific gene expression profiles in solid, adult tissues would benefit from approaches that avoid cellular stress during isolation. Here, we developed such an approach and identified highly selective transcriptomic signatures in adult mouse striatal direct and indirect spiny projection neurons, astrocytes, and microglia. Integrating transcriptomic and epigenetic data, we obtained a comprehensive model for cell-type-specific regulation of gene expression in the mouse striatum. A cross-analysis with transcriptomic and epigenomic data generated from mouse and human Huntington's disease (HD) brains shows that opposite epigenetic mechanisms govern the transcriptional regulation of striatal neurons and glial cells and may contribute to pathogenic and compensatory mechanisms. Overall, these data validate this less stressful method for the investigation of cellular specificity in the adult mouse brain and demonstrate the potential of integrative studies using multiple databases., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2019
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5. Long-term lentiviral-mediated expression of ciliary neurotrophic factor in the striatum of Huntington's disease transgenic mice

Author

Michael R. Hayden, Blair R. Leavitt, Nicole Déglon, Patrick Aebischer, Claire-Anne Gutekunst, Jean-Charles Bensadoun, Diana Zala, and Luís Pereira de Almeida

Subjects
Genetically modified mouse, Dopamine and cAMP-Regulated Phosphoprotein 32, medicine.medical_specialty, Pathology, Huntingtin, Ciliary neurotrophic factor, Transgene, Genetic Vectors, Gene Expression, Mice, Transgenic, Nerve Tissue Proteins, Motor Activity, Time, Mice, Gene therapy, Developmental Neuroscience, Internal medicine, Genetic model, medicine, Animals, Humans, Ciliary Neurotrophic Factor, Transgenes, Behavior, Animal, biology, Glial fibrillary acidic protein, HD transgenic mice, Lentivirus, Brain, Huntington's disease, Organ Size, Phosphoproteins, Corpus Striatum, Disease Models, Animal, Huntington Disease, Endocrinology, nervous system, Neurology, Disease Progression, biology.protein, Lentiviral vector, NeuN, Cell activation, Biomarkers
Abstract

Ciliary neurotrophic factor (CNTF) has been shown to prevent behavioral deficits and striatal degeneration in neurotoxic models of Huntington's disease (HD), but its effect in a genetic model has not been evaluated. Lentiviral vectors expressing the human CNTF or LacZ reporter gene were therefore injected in the striatum of wild-type (WT) and transgenic mice expressing full-length huntingtin with 72 CAG repeats (YAC72). Behavioral analysis showed increased locomotor activity in 5- to 6-month-old YAC72-LacZ mice compared to WT-LacZ animals. Interestingly, CNTF expression reduced the activity levels of YAC72 mice compared to control animals. In both WT and YAC72 mice, CNTF expression was demonstrated in striatal punches, up to a year after lentiviral injection. Stereological analysis revealed that the number of LacZ and DARPP-32-positive neurons were decreased in YAC72-LacZ mice compared to WT-LacZ animals. Assessment of the benefit of CNTF expression in the YAC72 mice was, however, complicated by a down-regulation of DARPP-32 and to a lesser extent of NeuN in all mice treated with CNTF. The expression of the neuronal marker NADPH-d was unaffected by CNTF, but expression of the astrocytic marker glial fibrillary acidic protein (GFAP) was increased. Finally, a reduction of the number of striatal dark cells was observed in YAC mice treated with CNTF compared to LacZ. These data indicate that sustained striatal expression of CNTF can be achieved with lentiviruses. Further studies are, however, needed to investigate the intracellular signaling pathways mediating the long-term effects of CNTF expression on dopamine signaling, glial cell activation and how these changes may affect HD pathology. http://www.sciencedirect.com/science/article/B6WFG-49Y3XT1-9/1/16c04560f4a6701364cee38ae0d31e5c

Published
2004

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