Glucocorticoid hormone (cortisol) affects axonal transport in human cortex neurons but shows resistance in Alzheimer's disease

<jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>The changes of tissue sensitivity to glucocorticoids are associated with many pathological states including neurological diseases. In the present study, using a novel <jats:italic>in vitro</jats:italic> 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.</jats:p></jats:list-item> <jats:list-item><jats:p>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 <jats:italic>μ</jats:italic>g dl<jats:sup>−1</jats:sup>.</jats:p></jats:list-item> <jats:list-item><jats:p>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 (<jats:italic>E</jats:italic><jats:sub>max</jats:sub>) on axonal transport was achieved in PFC slices at relatively low contraction (30–120 <jats:italic>μ</jats:italic>g dl<jats:sup>−1</jats:sup>), while in TC slices, a maximum effect was only reached at relatively high concentrations (120–240 <jats:italic>μ</jats:italic>g dl<jats:sup>−1</jats:sup>).</jats:p></jats:list-item> <jats:list-item><jats:p>For PFC and TC slices from nondemented aging subjects, lower doses of cortisol (30–60 <jats:italic>μ</jats:italic>g dl<jats:sup>−1</jats:sup>) 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 <jats:italic>μ</jats:italic>g dl<jats:sup>−1</jats:sup> of cortisol mostly depressed axonal transport.</jats:p></jats:list-item> <jats:list-item><jats:p>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.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2004) <jats:bold>143</jats:bold>, 606–610. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705995">10.1038/sj.bjp.0705995</jats:ext-link></jats:p>