Title:Long-Term Effects of Intracerebroventricular Streptozotocin Treatment on Adult Neurogenesis in the Rat Hippocampus
VOLUME: 12 ISSUE: 8
Author(s):Ping Sun, Ana Knezovic, Milena Parlak, Jacqueline Cuber, Margherita M. Karabeg, Jürgen Deckert, Peter Riederer, Qian Hua, Melita Salkovic-Petrisic and Angelika G. Schmitt
Affiliation:Center of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Füchsleinstr. 15, D-97080 Würzburg / Germany.
Keywords:Adult neurogenesis, hippocampus, intracerebroventricular, microglia, oligodendrocytes, sporadic Alzheimer`s
disease, streptozotocin.
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.
