title: Lipopolysaccharide has selective actions on sub-populations of catecholaminergic neurons involved in activation of the hypothalamic-pituitary-adrenal axis and inhibition of prolactin secretion.
abstract: Immune activation results in adaptive neuroendocrine responses, including activation of the hypothalamic-pituitary-adrenal axis, which are dependent on the integrity of medullary catecholaminergic (CA) systems. In contrast, although specific roles of pontine, midbrain, and hypothalamic CA systems in neuroendocrine function have been described, the functional roles of these CA systems in modulating neuroendocrine function during immune responses have not been investigated. We have, therefore, investigated the effects of immune activation on the various CA systems of the central nervous system (CNS) and explored this relationship with changes in plasma corticosterone and plasma prolactin. Male BALB/c mice were injected with lipopolysaccharide (LPS, 500 microg/kg i.p.) and 2 h later cardiac blood was taken and mice were perfused with fixative. Immunostaining procedures were performed using antibodies raised against c-Fos and tyrosine hydroxylase, a marker of CA neurons, and detailed topographical analysis of the CA systems within the CNS was performed. LPS-injected mice had increased concentrations of plasma corticosterone and decreased concentrations of plasma prolactin compared with vehicle-injected controls. LPS-injected mice had increased numbers of c-Fos-positive CA neurons within the medullary (A1, A2, C1, C2), pontine (A6) and midbrain (A10) cell groups when compared with vehicle-injected controls. Among hypothalamic CA cell groups, LPS had differential effects on the numbers of c-Fos-positive CA neurons in topographically organised subdivisions of the arcuate nucleus (A12). Changes in plasma prolactin concentrations correlated with the numbers of c-Fos-positive CA neurons within the area postrema, the medullary CA cell groups, the medial posterior division of the arcuate, and the zona incerta. The present study identifies topographically organised, anatomically distinct CA systems that are likely to modulate some of the neuroendocrine responses to immune activation, and may provide novel targets for the relief of symptoms associated with illness and disease.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (HWLINE), University of Bristol, Dorothy Hodgkin Building (DHB), Whitson Street, Bristol BS1 3NY, United Kingdom. jhollis@bristol.ac.uk
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Hollis
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D008070:Lipopolysaccharides; D011388:Prolactin; D003345:Corticosterone