title: Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration.
abstract: The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer's disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases.
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK d.gomez-nicola@soton.ac.uk.
authors.forename: Diego
authors.initials: D
authors.lastname: Gomez-Nicola
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Suzzi
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Mariana
authors.initials: M
authors.lastname: Vargas-Caballero
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Nina L
authors.initials: NL
authors.lastname: Fransen
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Hussain
authors.initials: H
authors.lastname: Al-Malki
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Cebrian-Silla
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Riecken
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
authors.affiliation: 1 Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation; D002908:Chronic Disease; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005822:Genetic Vectors; D006624:Hippocampus / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D019599:Mossy Fibers, Hippocampal / Q000648:ultrastructure; D009434:Neural Pathways / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D056347:Neuroanatomical Tract-Tracing Techniques; D019636:Neurodegenerative Diseases / Q000473:pathology*; D055495:Neurogenesis / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017096:Prion Diseases / Q000473:pathology*; D011328:Prions / Q000472:pathogenicity; D013997:Time Factors; D014015:Tissue Banks; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D011328:Prions; D003561:Cytarabine
keywords: Alzheimer’s disease; adult neurogenesis; neural stem cells; variant CJD