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Expansion of the Golgi apparatus in rat cerebral cortex following intracerebroventricular injections of streptozotocin

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Grieb P., Kryczka T., Fiedorowicz M., Frontczak-Baniewicz M., Walski M.

Acta Neurobiologiae Experimentalis

2004

vol. 64

issue 4

481-489

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 ? 103 nm3 in 14 neurons from control animals, and 846 ? 103 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.

2-Deoxyglucose induces beta-APP overexpression, tau hyperphosphorylation and expansion of the trans-part of the Golgi complex in rat cerebral cortex

59%

Grieb P., Gordon-Krajcer W., Frontczak-Baniewicz M., Walski M., Ryba M. S., Kryczka T., Fiedorowicz M., Kulinowski P., Sulek Z., Majcher K., Jasinski A.

Acta Neurobiologiae Experimentalis

2004

vol. 64

issue 4

491-502

The effects of a single intraperitoneal injection of a non-metabolizable glucose analog 2-deoxyglucose (2-DG, 500 mg/kg) on the levels of b-APP expression, and phosphorylated and unphosphorylated tau protein in the rat cerebral cortex were investigated. The effects of 2-DG on the ultrastructure of cortical neurons with particular emphasis on the morphology of the Golgi apparatus, and on brain bioenergetics assessed by in vivo 31P-MRS technique were also evaluated. Seven and a half hours after injection of 2-deoxyglucose a significant increase in brain cortex b-APP expression, increased tau phosphorylation, and a marked relative expansion of the trans- part of the Golgi intracellular secretory pathway in cortical neurons has been found. The changes of b-APP expression and tau phosphorylation appeared within 1 h after 2-DG application and continued for at least 24 h. However, brain 31P resonance spectra remained unchanged for up to 7.5 h after 2-DG. It is suggested that the increase of b-APP expression represents a response of brain tissues to 2-DG-evoked biochemical stress, while tau hyperphosphorylation and the change in Golgi morphology may be secondary phenomena.

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2 Acta Neurobiologiae Experimentalis

2 2004

2 Fiedorowicz M.

2 Frontczak-Baniewicz M.

2 Grieb P.

2 Kryczka T.

2 Walski M.

1 Gordon-Krajcer W.

1 Jasinski A.

1 Kulinowski P.

1 Majcher K.

1 Ryba M. S.

1 Sulek Z.

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Expansion of the Golgi apparatus in rat cerebral cortex following intracerebroventricular injections of streptozotocin

2-Deoxyglucose induces beta-APP overexpression, tau hyperphosphorylation and expansion of the trans-part of the Golgi complex in rat cerebral cortex