Intracerebroventricular injection of streptozotocin causes neurotoxicity to myelin that contributes to spatial memory deficits in rats.
It has been reported that intracerebroventricular (icv) injection of streptozotocin (STZ) impairs spatial memory by disrupting glucose utilization through an insulin-dependent mechanism in the cerebral cortex and hippocampus. However, evidence of septal damage and microglosis induced by icv STZ suggested that its neurotoxic effects could contribute to the memory impairment. The present study examined the histopathological changes in adult rats following three icv STZ injections (0.25 mg into each lateral ventricle) and their effects on spatial memory in a Morris water maze task. STZ retarded acquisition of reference learning (progressive reduction in escape latency) and disrupted working memory (difference in escape latency between the two swims within a daily session). STZ caused selective injury to myelin and axons in the fornix and hippocampus in association with activation of microglia. The 3rd ventricle was enlarged by 100-150% because of a loss of ependymal cells and damage to hypothalamic periventricular myelin but the process involved in these changes is unclear. Our findings provide an alternative explanation for the decrease in glucose utilization in the hippocampus and cortex and the impairment of spatial memory induced by STZ. These could result from a disruption of the communication through myelinated axons in the fornix connecting the septum and the hippocampus, and through other myelinated axons adjacent to the ventricles. The selective damage to myelin may well result from oxidative stress.
Shoham
S
S
Research Department, Herzog Hospital, School of Pharmacy, Hebrew University Medical Centre, Jerusalem, Israel.
Bejar
C
C
Kovalev
E
E
Weinstock
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology*; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D013311:Streptozocin / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D013311:Streptozocin