GISNe - Anatomia, Farmacologia e Medicina Legale

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MENOPAUSAL TRANSITION: A POSSIBLE RISK FACTOR FOR NEURODEGENERATIVE EVENTS Sara Maria Bonomo Dipartimento di <strong>Farmacologia</strong>, Chemioterapia e Tossicologia Medica, Università degli Studi di Milano Background and objective. Incidence and prevalence of Alzheimer Disease (AD) are higher in postmenopausal women than in aged matched men. Since at menopause the endocrine system and other biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegdedly neuroprotective (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered proneurotoxic (e.g. related to glucocorticoids and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders. Subjects and Methods. Along this aim, we investigated in 209 healthy subjects (73 M, 106 F, 20- 91 yr-old) and 85 AD patients (36 M, 49 F, 65-89 yr-old) the gene expression of estrogen receptors (ERs), glucocorticoid receptors (GRs), interleukin-6 (IL-6) and CD36, a scavenger receptor of class B that would play a key role in the proinflammatory events associated with AD. Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells: 1) are easily obtainable by a simple blood sampling, 2) express many molecules and multiple receptors which undergo the same regulatory mechanisms as those operative in the brain and 3) share many function with microglial cells. Results. In healthy men all the study parameters remained quite stable during lifespan.() In women, instead, at menopausal transition some changes occurred that may predispose to neurodegeneration. In particular, there was: 1) up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol; 2) an augmentation of GRα:GRβ ratio, indicative of an augmented cortisol activity on GRα not sufficiently counteracted by the inhibitory GRβ function; 3) a reduced CD36 expression directly related to the increased cortisol activity and, 4) an augmented cortisol:DHEAS ratio, unanimously recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of either sex, the expression of the study parameters was similar to that found in sex- and agematched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events. Specificare l’andamento nell’uomo. Conclusions. Menopausal transition is a critical phase of women’s life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part,
from the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers.
Page 1 and 2: GRUPPO ITALIANO DI SCIENZE NEUROEND
Page 3 and 4: GIULIA D'INTINO (BOLOGNA) UTILIZZO
Page 5 and 6: MARCO LUPPI (BOLOGNA) STUDIO DELLA
Page 7 and 8: Il Leukemia Inhibitory Factor induc
Page 9 and 10: ORMONI TIROIDEI NEI PAZIENTI EPILET
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Page 13 and 14: MATERNAL THYROID HORMONES ARE TRANS
Page 15: differenziate in senso neuronale (h
Page 19 and 20: Modificazioni dell’espressione ge
Page 21 and 22: DIFFERENT INFLUENCES OF OVARIAN AND
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Page 25 and 26: Effetti degli xenoestrogeni sul dif
Page 27 and 28: Interazioni neuroendocrino-immunolo
Page 29 and 30: INDIVIDUAL DIFFERENCES IN CARDIAC A
Page 31 and 32: REGOLAZIONE NEUROENDOCRINA ED AMBIE
Page 33 and 34: Calcium channels-secretion coupling
Page 35 and 36: voluto verificare se differenti sch
Page 37 and 38: SISTEMA SEROTONINERGICO E REGOLAZIO
Page 39 and 40: Patologie endocrino-metaboliche e a
Page 41 and 42: RETINOIDS AND DOPAMINE RECEPTOR SUB
Page 43: SOMATOSTATIN ANALOGUES AND GHRH ANT

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