title: Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin.
abstract: 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 14(th) 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Paidi
authors.forename: Dominic N
authors.initials: DN
authors.lastname: Nthenge-Ngumbau
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Singh
authors.forename: Thulasi
authors.initials: T
authors.lastname: Kankanala
authors.forename: Hina
authors.initials: H
authors.lastname: Mehta
authors.affiliation: Laboratory of Clinical & Experimental Neuroscience, Division of cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India. kpmohanakumar@yahoo.com.
authors.forename: Kochupurackal P
authors.initials: KP
authors.lastname: Mohanakumar
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D018782:Maze Learning / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000150:complications; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000903:Antibiotics, Antineoplastic; D001786:Blood Glucose; D009419:Nerve Tissue Proteins; C095992:complexin I; D013311:Streptozocin; D002795:Choline O-Acetyltransferase; D002950:Citrate (si)-Synthase