Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA

B Marchetti, M C Morale, N Testa, C Tirolo, S Caniglia, S Amor, C D Dijkstra, N Barden

Research output: Contribution to journalReview articleAcademicpeer-review

47 Citations (Scopus)


Current research evidence suggests that interactions between genetic and environmental factors contribute to modulate the susceptibility to degenerative disorders, including inflammatory and autoimmune diseases of the central nervous system (CNS). In this context, bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life, thereby influencing the predisposition to several disease entities. Glucocorticoids (GCs), the end products of the hypothalamic-pituitary-adrenocortical (HPA) axis, gender and signals generated by hypothalamic-pituitary-gonadal (HPG) axis are major players coordinating the development of immune system function and exerting powerful effects in the susceptibility to autoimmune disorders, including experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS). In particular, GCs exert their beneficial immunosuppressive and anti-inflammatory effects in inflammatory disorders of the CNS, after binding to their cytoplasmic receptors (GRs). Here we review our work using transgenic (Tg) mice with a dysfunctional GR from early embryonic life on programming vulnerability to EAE. The GR-deficiency of these Tg mice confers resistance to active EAE induction. The interplay between GCs, proinflammatory mediators, gender and EAE is summarized. On the basis of our data, it does appear that exposure to a defective GR through development programs major changes in endogenous neuroendocrine and immune mechanisms controlling the vulnerability to EAE. These studies highlight the plasticity of the HPA-immune axis and its pharmacological manipulation in autoimmune diseases of the CNS.

Original languageEnglish
Pages (from-to)259-72
Number of pages14
JournalBrain Research Bulletin
Issue number1-3
Publication statusPublished - Nov 2001


  • Animals
  • Autoimmunity
  • Central Nervous System
  • Genetic Predisposition to Disease
  • Journal Article
  • Macrophages
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • RNA, Antisense
  • Receptors, Glucocorticoid
  • Research Support, Non-U.S. Gov't
  • Review
  • Sex Factors
  • Stress, Physiological
  • T-Lymphocytes

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