Expansion of the Golgi apparatus in rat cerebral cortex following intracerebroventricular injections of streptozotocin.
Streptozotocin (STZ) is a bacterial toxin which selectively damages both insulin-producing cells and insulin receptors. Injections of STZ into the cerebral ventricles of experimental animals are followed by sustained biochemical, metabolic and behavioral effects resembling those which are found in human brains afflicted by Alzheimer's disease. The aim of the present study was to assess the effects of double intracerebroventricular application of STZ on the ultrastructure of rat frontoparietal cortical neurons. The most prominent change, seen 3 weeks after STZ injection, was a significant enlargement of the Golgi apparatus caused by expansion of the trans-Golgi segment of the cellular protein secretory pathway. Morphometric analysis revealed that the area of the trans part of the Golgi complex in neuronal cells was increased more than two-fold (median values: 312 x 10(3) nm in 14 neurons from control animals, and 846 x 10(3) nm3 in 19 neurons from STZ-treated animals, P = 0.0012), whereas that of the cis part did not significantly change. The effects of STZ did not resemble Golgi atrophy and fragmentation described in neurons from disease-prone brain structures of patients with Alzheimer's disease, but were similar to that observed after intravenous application of a non-metabolizable glucose analog 2-deoxyglucose. Considering that proamyloidogenic processing of beta-amyloid precursor protein may occur preferentially in the trans-Golgi segment, the observed early response of neuronal ultrastructure to desensitization of insulin receptors may predispose cells to form beta-amyloid deposits.
Grieb
Paweł
P
Department of Experimental Pharmacology, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland. pgrieb@cmdik.pan.pl.
Kryczka
Tomasz
T
Fiedorowicz
Michał
M
Frontczak-Baniewicz
Małgorzata
M
Walski
Michał
M
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D006056:Golgi Apparatus / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D007276:Injections, Intraventricular / Q000379:methods*; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity*
D013311:Streptozocin