PMID- 14769399
OWN - NLM
STAT- MEDLINE
DCOM- 20040402
LR  - 20131121
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 184
IP  - 2
DP  - 2003 Dec
TI  - Intracerebroventricular injection of streptozotocin causes neurotoxicity to 
      myelin that contributes to spatial memory deficits in rats.
PG  - 1043-52
AB  - 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.
FAU - Shoham, S
AU  - Shoham S
AD  - Research Department, Herzog Hospital, School of Pharmacy, Hebrew University 
      Medical Centre, Jerusalem, Israel.
FAU - Bejar, C
AU  - Bejar C
FAU - Kovalev, E
AU  - Kovalev E
FAU - Weinstock, M
AU  - Weinstock M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 5W494URQ81 (Streptozocin)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*administration & dosage
MH  - Injections, Intraventricular
MH  - Lateral Ventricles/drug effects/pathology/physiopathology
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Memory/drug effects/physiology
MH  - Memory Disorders/chemically induced/*physiopathology
MH  - Myelin Sheath/*drug effects/pathology
MH  - Neurons/*drug effects/pathology
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spatial Behavior/drug effects/physiology
MH  - Streptozocin/*administration & dosage
EDAT- 2004/02/11 05:00
MHDA- 2004/04/03 05:00
CRDT- 2004/02/11 05:00
PHST- 2003/04/04 00:00 [received]
PHST- 2003/08/04 00:00 [revised]
PHST- 2003/08/08 00:00 [accepted]
PHST- 2004/02/11 05:00 [pubmed]
PHST- 2004/04/03 05:00 [medline]
PHST- 2004/02/11 05:00 [entrez]
AID - S0014488603004175 [pii]
AID - 10.1016/j.expneurol.2003.08.015 [doi]
PST - ppublish
SO  - Exp Neurol. 2003 Dec;184(2):1043-52. doi: 10.1016/j.expneurol.2003.08.015.