What mouse mutants and chimeras can tell us about compartmentation and development of the mammalian nervous system

Abstract

Neurotrophins including nerve growth factor (NGF) are clearly multifunctional and increasing evidence indicates that NGF, in addition to its neurotrophic actions, regulates and is regulated by components of the immune system. In support of this expression of functional trk protooncogene is found, constituting the signal transducing receptor for NGF, on monocytes and lymphocytes. In addition, a possible pathophysiological role for NGF in autoimmune disorders is suggested by the findings that NGF levels are markedly raised in cerebrospinal fluid of patients with multiple sclerosis (MS) and in serum of patients with systemic lupus erythematosus (SLE). As yet, it is completely unknown whether other members of the NGF-like neurotrophin (NT) family, such as brain-derived neurotrophic factor, NT-3, and NT-4/5 are also involved in modulation of immune system responses. Experiments and others provide evidence for a significant degree of interaction between the nervous and immune systems. If such communication is physiologically important, then disturbances in homeostasis and in cross-talk between these systems would conceivably effect pathological changes leading, eventually, to neurodegenerative and autoimmune disorders.