title: Long-Term Effects of Intracerebroventricular Streptozotocin Treatment on Adult Neurogenesis in the Rat Hippocampus.
abstract: Altered adult hippocampal neurogenesis (AN) plays a role in the etiopathology of Alzheimer's disease (AD), a disorder characterized by a progressive loss of memory and spatial orientation impairment. Diabetes is shown to be one risk factor for the development of the sporadic form of AD (sAD), which affects >95% of AD patients. Streptozotocin intracerebroventricularily (STZ icv) treated rats, which develop an insulin-resistant brain state and learning and memory deficits preceding amyloid beta and tau pathology, may act as an appropriate animal model for sAD. The goal of our quantitative immunohistochemistry study was to compare short-term (1 month) and long-term (3 months) effects of STZ icv treatment on different AN stages. Applying MCM2 antibodies we quantified cell (e.g. stem cell) proliferation, by the use of NeuroD and DCX antibodies we analyzed immature neurons. BrdU incorporation with approximately 27 days of survival before sacrifice allowed us to quantify and identify surviving newborn cells. Performing co-localization studies with antibodies detecting BrdU and cell-type specific markers we could confirm that STZ treatment does not affect the differentiation fate of newly generated cells. Whereas STZ icv treatment does not seem to considerably influence cell proliferation over a shortterm period (1 month), in the long-term (3 months) it significantly decreased generation of immature and mature neurons. This reduction seen after 3 months was specific for the septal hippocampus, discussed to be important for spatial learning. Moreover, AN changes display the same timeline as the development of amyloid beta pathology in this animal model of sAD.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Ana
authors.initials: A
authors.lastname: Knezovic
authors.forename: Milena
authors.initials: M
authors.lastname: Parlak
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cuber
authors.forename: Margherita M
authors.initials: MM
authors.lastname: Karabeg
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Qian
authors.initials: Q
authors.lastname: Hua
authors.forename: Melita
authors.initials: M
authors.lastname: Salkovic-Petrisic
authors.affiliation: Center of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Füchsleinstr. 15, D-97080 Würzburg / Germany. Schmitt_A3@ukw.de.
authors.forename: Angelika G
authors.initials: AG
authors.lastname: Schmitt
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013311:Streptozocin / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D009419:Nerve Tissue Proteins; D013311:Streptozocin; D001973:Bromodeoxyuridine