Background: Bilateral intracerebroventricular (ICV) administration of streptozotocin (STZ)
causes Alzheimer’s disease (AD)-type neurodegeneration in rats. The model is increasingly used for
investigating pathology and therapeutic strategies for AD. Objective: The present study investigated
cognitive abilities in rats infused with STZ-ICV in relation to hippocampal and cortical mitochondrial
functions during a period of 60 days. Methods: Cognitive functions were assayed in rats employing
various mazes. Mitochondrial state-3-respiration, complex-I activity and dynamin related protein-1
(DRP-1) expression were measured respectively by oxygraph, spectrophotometry and immunoblot assay.
Amyloidosis was investigated employing Congo red staining. Results: One-time ICV-STZ infused animals exhibited
body-weight loss and impaired cognitive ability from 14th day post-infusion. A significant loss of mitochondrial electron
transport chain complex-I activity in the hippocampi and cortices was found by 14 days, and persisted up to 60 days following
ICV-STZ infusion. Mitochondrial state-3 respiration was unaltered in these brain regions by 14 days, but significantly
decreased from 21 days after STZ administration. DRP-1 expression was significantly increased in the hippocampi
and cortices of these animals 21 days after infusion, but persisted only in the hippocampi up to 60 days. Congophilic
granules indicative of amyloidosis were detected in the hippocampus by 21 days. Conclusion: Our results suggest that the
non-genetic sporadic AD (sAD) rat model developed by single-time STZ-ICV infusion exhibits protein aggregation and
dementia probably resulting from increased mitochondrial fragmentation and functional aberrations. The present study reinforces
the validity of this model for studying pathogenesis and potential therapies of sAD.
Keywords: Amyloidosis, cognitive functional loss, dynamin related protein 1, mitochondrial respiratory loss, non-transgenic
animal model, sporadic Alzheimer’s disease model.
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