Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide.
The central nervous system interacts with the immune system to coordinate several components of the acute phase response, although the specific neuroanatomical pathways that mediate these responses are still uncharacterized. However, neurons in both the autonomic and endocrine components of the paraventricular hypothalamic nucleus (PVH) are characteristically activated in different models of immune stimulation. In the current study, we have used intravenous administration of lipopolysaccharide (LPS; 5 or 125 micrograms/kg) to induce the acute phase response. We subsequently coupled immunohistochemistry for Fos (as a marker of neuronal activation) with retrograde transport of the neuroanatomical tracer cholera toxin-b from the PVH. Several of the activated cell groups directly projected to the paraventricular nucleus, including the visceromotor (infralimbic) cortex, median preoptic nucleus, ventromedial preoptic area, bed nucleus of the stria terminalis, parabrachial nucleus, ventrolateral medulla, and nucleus of the solitary tract. These findings indicate that immune system stimulation activates cell groups from multiple nervous system levels that project to the paraventricular nucleus. We hypothesize that the activation of specific autonomic and endocrine elements of the PVH may be due to the activity of distinct afferents that converge on the PVH from multiple components of the central autonomic control system. Our results are consistent with the hypothesis that the PVH plays a key role in integrating diverse physiological cues into the varied manifestations that constitute the cerebral component of the acute phase response.
Department of Neurology, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02115, USA. jelmquis@bih.harvard.edu
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Elmquist
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Saper
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000818:Animals; D017776:Autonomic Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002772:Cholera Toxin / Q000633:toxicity; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D002772:Cholera Toxin