Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo

Elicia M. Elliott, Mark P. Mattson, Peter Vanderklish, Gary Lynch, Ingrid Chang, Robert M. Sapolsky

Research output: Contribution to journalArticle

Abstract

Aberrant elevations in intracellular calcium levels, promoted by the excitatory amino acid glutamate, may be a final common mediator of the neuronal damage that occurs in hypoxic-ischemic and seizure disorders. Glutamate and altered neuronal calcium homeostasis have also been proposed to play roles in more chronic neurodegenerative disorders, including Alzheimer's disease. Any extrinsic factors that may augment calcium levels during such disorders may significantly exacerbate the resulting damage. Glucocorticoids (GCs), the adrenal steroid hormones released during stress, may represent one such extrinsic factor. GCs can exacerbate hippocampal damage induced by excitotoxic seizures and hypoxia-ischemia, and we have observed recently that GCs elevate intracellular calcium levels in hippocampal neurons. We now report that the excitotoxin kainic acid (KA) can elicit antigenic changes in the microtubule-associated protein tau similar to those seen in the neurofibrillary tangles of Alzheimer's disease. KA induced a transient increase in the immunoreactivity of hippocampal CA3 neurons towards antibodies that recognize aberrant forms of tau (5E2 and Alz-50). The tau immunoreactivity appeared within 3 h of KA injection, preceded extensive neuronal damage, and subsequently disappeared as neurons degenerated. KA also caused spectrin breakdown, indicating the involvement of calcium-dependent proteases. Physiological concentrations of corticosterone (the species-typical GC of rats) enhanced the neuronal damage induced by KA and, critically, enhanced the intensity of tau immunoreactivity and spectrin breakdown. Moreover, the GC enhancement of spectrin proteolysis was prevented by energy supplementation, supporting the hypothesis that GC disruption of calcium homeostasis in the hippocampus is energetic in nature. Taken together, these findings demonstrate that neurofibrillary tangle-like alterations in tau, and spectrin breakdown, can be induced by excitatory amino adds and exacerbated by GCs in vivo.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalJournal of Neurochemistry
Volume61
Issue number1
StatePublished - 1993
Externally publishedYes

Fingerprint

Proteolysis
Spectrin
Kainic Acid
Corticosterone
Glucocorticoids
Calcium
Neurons
Neurofibrillary Tangles
Glutamic Acid
Alzheimer Disease
Homeostasis
Steroid hormones
Excitatory Amino Acids
Microtubule-Associated Proteins
Neurotoxins
Neurodegenerative Diseases
Rats
Epilepsy
Hippocampus
Seizures

Keywords

  • Alzheimer'sdisease
  • Corticosterone
  • Cytosketeton
  • Spectrin
  • Stress
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Elliott, E. M., Mattson, M. P., Vanderklish, P., Lynch, G., Chang, I., & Sapolsky, R. M. (1993). Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo. Journal of Neurochemistry, 61(1), 57-67.

Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo. / Elliott, Elicia M.; Mattson, Mark P.; Vanderklish, Peter; Lynch, Gary; Chang, Ingrid; Sapolsky, Robert M.

In: Journal of Neurochemistry, Vol. 61, No. 1, 1993, p. 57-67.

Research output: Contribution to journalArticle

Elliott, EM, Mattson, MP, Vanderklish, P, Lynch, G, Chang, I & Sapolsky, RM 1993, 'Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo', Journal of Neurochemistry, vol. 61, no. 1, pp. 57-67.
Elliott, Elicia M. ; Mattson, Mark P. ; Vanderklish, Peter ; Lynch, Gary ; Chang, Ingrid ; Sapolsky, Robert M. / Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo. In: Journal of Neurochemistry. 1993 ; Vol. 61, No. 1. pp. 57-67.
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