Neural progenitor cells attenuate inflammatory reactivity and neuronal loss in an animal model of inflamed AD brain
Notice bibliographique
Résumé
BACKGROUND: Transplantation of neural progenitor cells (NPC) constitutes a putative therapeutic maneuver for use in treatment of neurodegenerative diseases. At present, effects of NPC transplantation in Alzheimer's disease (AD) brain are largely unknown and a primary objective of this work was to demonstrate possible efficacy of NPC administration in an animal model of AD. The benefits of transplantation could involve a spectrum of effects including replacement of endogenous neurons or by conferring neuroprotection with enhancement of neurotrophic factors or diminishing levels of neurotoxic agents. Since chronic inflammation is a characteristic property of AD brain, we considered that transplantation of NPC could have particular utility in inhibiting ongoing inflammatory reactivity. We have tested intrahippocampal transplantation of NPC for efficacy in attenuating inflammatory responses and for neuroprotection in beta-amyloid (Abeta1-42) peptide-injected rat hippocampus. METHODS: Spheres of neural progenitor cells were grown from dissociated telencephalon tissue of rat embryos. NPC were infected with lentiviral vector green fluorescent protein (GFP) with subsequent cell transplantation into rat hippocampus previously injected (3 d prior) with Abeta1-42 peptide or PBS control. Immunohistochemical analysis was carried out (7 d post-NPC transplantation, 10 d post-peptide/PBS injection) for GFP, microgliosis (Iba-1 marker), astrogliosis (GFAP marker), neuron viability (MAP-2 marker) and levels of the proinflammatory cytokine, TNF-alpha. RESULTS: Successful infection of cultured NPC with lentiviral vector green fluorescent protein (GFP) was demonstrated prior to cell transplantation into rat hippocampus. In vivo, immunohistochemical staining showed migration of GFP-positive cells, in a region of dentate gyrus between Abeta1-42/PBS injection site and NPC transplantation site, was increased x2.8-fold with Abeta1-42 compared to PBS injection. Double immunostaining in peptide-injected brain indicated GFP association with nestin and GFAP, but not MAP-2. Cell-specific immunostaining showed marked increases in microgliosis and astrogliosis in Abeta1-42-injected brain (respective increases of x4.3- and x4.6-fold compared with PBS injection). NPC transplantation significantly reduced microgliosis (by 38%) but not astrogliosis in peptide-injected hippocampus. The proinflammatory cytokine TNF-alpha was elevated by 6.7-fold (peptide vs PBS injection) with NPC administration attenuating levels of TNF-alpha (by 40%). Peptide-injected brain demonstrated neuronal loss (MAP-2 staining reduced by 45% vs PBS injection) with NPC transplantation effective in conferring neuroprotection (26% recovery of neurons). CONCLUSIONS: These findings indicate efficacy for NPC transplantation in an animal model of AD with effects consistent with cellular actions to attenuate inflammatory reactivity induced by intrahippocampal peptide injection.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,002 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».