title: Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.
abstract: Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease) and brain traumas (stroke, epilepsy, and traumatic brain injury). One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A) mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery.
authors.affiliation: Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Myczek
authors.affiliation: Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Yeung
authors.affiliation: Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Castello
authors.affiliation: Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Baglietto-Vargas
authors.affiliation: Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America.
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology*; D004167:Diphtheria Toxin / Q000096:biosynthesis / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*
chemical_list: D004167:Diphtheria Toxin; D011993:Recombinant Fusion Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004318:Doxycycline