title: Hippocampal neuronal subtypes develop abnormal dendritic arbors in the presence of Fragile X astrocytes.
abstract: Astrocytes are now recognized as key players in the neurobiology of neurodevelopmental disorders such as Fragile X syndrome. However, the nature of Fragile X astrocyte-mediated control of dendrite development in subtypes of hippocampal neurons is not yet known. We used a co-culture procedure in which wildtype primary hippocampal neurons were cultured with astrocytes from either a wildtype or Fragile X mouse, for either 7, 14 or 21 days. The neurons were processed for immunocytochemistry with the dendritic marker MAP2, classified by morphological criteria into one of five neuronal subtypes, and subjected to Sholl analyses. Both linear and semi-log methods of Sholl analyses were applied to the neurons in order to provide an in depth analysis of the dendritic arborizations. We found that Fragile X astrocytes affect the development of dendritic arborization of all subtypes of wildtype hippocampal neurons. Furthermore, we show that hippocampal neurons with spiny stellate neuron morphology exhibit the most pervasive developmental delays, with significant dendritic arbor alterations persisting at 21 days in culture. The results further dictate the critical role astrocytes play in governing neuronal morphology including altered dendrite development in Fragile X.
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Jacobs
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: doering@mcmaster.ca.
authors.forename: L C
authors.initials: LC
authors.lastname: Doering
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003712:Dendrites / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D008869:Microtubule-Associated Proteins; C497684:Fmr1 protein, mouse; C079240:Mtap2 protein, mouse
keywords: FMRP; Fragile X; arborization; astrocyte; dendrite; neuron