Glucocorticoid hormone (cortisol) affects axonal transport in human cortex neurons but shows resistance in Alzheimer's disease.
1 The changes of tissue sensitivity to glucocorticoids are associated with many pathological states including neurological diseases. In the present study, using a novel in vitro post-mortem tracing method on human brain slices, we demonstrated that cortisol, a major glucocorticoid hormone in humans, affected axonal transport both in the cortex neurons in four Alzheimer's disease (AD) patients and four nondemented controls. 2 Cortisol appeared to affect axonal transport of prefrontal cortex (PFC) and temporal cortex (TC) neurons in AD patients and controls in a dose-dependent way at concentrations of 30, 60, 120 and 240 microg dl(-1). 3 Higher doses of cortisol were needed for TC neurons to achieve a similar axonal transport effect as obtained in PFC neurons in AD patients. The maximum effect (Emax) on axonal transport was achieved in PFC slices at relatively low contraction (30-120 microg dl(-1)), while in TC slices, a maximum effect was only reached at relatively high concentrations (120-240 microg dl(-1)). 4 For PFC and TC slices from nondemented aging subjects, lower doses of cortisol (30-60 microg dl(-1)) on axonal transport were sufficient to achieve the maximum effect as compared to those used in AD brain slices, while levels of more than 60 microg dl(-1) of cortisol mostly depressed axonal transport. 5 These results suggest that glucocorticoid resistance, which is thought to contribute to the pathogenesis of a number of common human disorders, may exist in AD brains and play an important role in neuropathological mechanisms and dementia.
Dai
Jiapei
J
The Netherlands Institute for Brain Research, Amsterdam, The Netherlands. J.dai@nih.knaw.nl
Buijs
Ruud
R
Swaab
Dick
D
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D001370:Axonal Transport / Q000187:drug effects*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism / Q000473:pathology
D006854:Hydrocortisone