The effect of insulin deficiency on tau and neurofilament in the insulin knockout mouse

Ruben Schechter, Delia Beju, Kenneth E. Miller

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Complications of diabetes mellitus within the nervous system are peripheral and central neuropathy. In peripheral neuropathy, defects in neurofilament and microtubules have been demonstrated. In this study, we examined the effects of insulin deficiency within the brain in insulin knockout mice (I(-/-)). The I(-/-) exhibited hyperphosphorylation of tau, at threonine 231, and neurofilament. In addition, we showed hyperphosphorylation of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 β (GSK-3 β) at serine 9. Extracellular signal-regulated kinase 1 (ERK 1) showed decrease in phosphorylation, whereas ERK 2 showed no changes. Ultrastructural examination demonstrated swollen mitochondria, endoplasmic reticulum, and Golgi apparatus, and dispersion of the nuclear chromatin. Microtubules showed decrease in the number of intermicrotubule bridges and neurofilament presented as bunches. Thus, lack of insulin brain stimulation induces JNK hyperphosphorylation followed by hyperphosphorylation of tau and neurofilament, and ultrastructural cellular damage, that over time may induce decrease in cognition and learning disabilities.

Original languageEnglish
Pages (from-to)979-986
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume334
Issue number4
DOIs
StatePublished - 9 Sep 2005

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Intermediate Filaments
Knockout Mice
Insulin
Brain
Peripheral Nervous System Diseases
Microtubules
Glycogen Synthase Kinase 3
Phosphorylation
Mitochondria
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Neurology
Threonine
Medical problems
Serine
Chromatin
Learning Disorders
Golgi Apparatus
Phosphotransferases
Diabetes Complications

Keywords

  • Brain
  • Diabetes
  • ERK
  • Electron microscopy
  • GSK-3
  • Insulin
  • Insulin knockout mice
  • JNK
  • Neurofilament
  • Tau

Cite this

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The effect of insulin deficiency on tau and neurofilament in the insulin knockout mouse. / Schechter, Ruben; Beju, Delia; Miller, Kenneth E.

In: Biochemical and Biophysical Research Communications, Vol. 334, No. 4, 09.09.2005, p. 979-986.

Research output: Contribution to journalArticle

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