ABSTRACT
In a previous study, we found that microinjection of the cytokine interleukin-1 (IL-1) into the locus coeruleus (LC) increased the electrophysiological activity of LC neurons. To determine if endogenous IL-1 similarly affects the LC, brain IL-1 was induced with lipopolysaccharide (LPS), a substance derived from Gram-negative bacteria. LPS microinjected directly into the LC increased the activity of LC neurons in anesthetized rats, and this effect was blocked by microinfusion of the IL-1 receptor antagonist (IL-1RA) protein into the LC indicating the involvement of IL-1 receptors. Similarly, intraperitoneal (i.p.) LPS injection increased the activity of LC neurons in a dose- and time-related manner that was sensitive to IL-1RA. The change in the activity of LC neurons caused by a single i.p. injection of LPS was surprisingly long-lasting, and evolved over a period of at least 3 weeks. Other microbial substances-namely, peptidoglycan from Gram-positive bacteria and poly-inosine/poly-cytosine (poly(I)/(C)), which resembles RNA viruses-were used to determine the generality of the findings with LPS. Both i.p. peptidoglycan and poly(I)/(C) increased LC activity but with lesser efficacy than LPS. IL-1RA reversed the increase in the activity of LC neurons caused by i.p. peptidoglycan treatment; however, that caused by i.p. Poly(I)/(C) was not diminished by IL-1RA. Thus, the increased activity of LC neurons caused by LPS and peptidoglycan requires IL-1 receptor binding, suggesting the involvement of endogenously-produced IL-1. In contrast, poly(I)/(C) increased the activity of LC neurons but this did not critically involve IL-1 receptors in the LC.
Subject(s)
Interleukin-1/physiology , Lipopolysaccharides/pharmacology , Locus Coeruleus/cytology , Neurons/drug effects , Peptidoglycan/pharmacology , Action Potentials/drug effects , Analysis of Variance , Animals , Dose-Response Relationship, Drug , Drug Administration Routes , Drug Interactions , Female , Injections, Intraperitoneal/methods , Interleukin 1 Receptor Antagonist Protein , Interleukin-1/metabolism , Locus Coeruleus/microbiology , Locus Coeruleus/virology , Microinjections/methods , Neurons/microbiology , Neurons/physiology , Neurons/virology , Physical Stimulation/methods , Rats , Rats, Sprague-Dawley , Sialoglycoproteins/administration & dosage , Time FactorsABSTRACT
The spread of mouse hepatitis virus, strain JHM and herpes simplex virus type 1 in the central nervous system after inoculation into the nares and main olfactory bulb has been examined. The results show that each virus infects a subset of the possible connections of the olfactory bulb and that the subset infected by each virus is different. Thus, both viruses will be useful for studying the neuroanatomic connections of the olfactory bulb, and possibly for functional analyses as well.
Subject(s)
Dental Pulp/microbiology , Murine hepatitis virus/physiology , Olfactory Bulb/microbiology , Olfactory Pathways/microbiology , Simplexvirus/physiology , Trigeminal Nerve/microbiology , Administration, Intranasal , Animals , Axonal Transport , Brain/microbiology , Brain/ultrastructure , Injections , Locus Coeruleus/microbiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Species Specificity , Specific Pathogen-Free OrganismsABSTRACT
I have presented a possible case of mania induced by influenza B. Some epidemic influenza viruses may be neurovirulent. These epidemics seem to be associated with postencephalitic Parkinson's disease, mania, and depression. Viral, neuroanatomic, neurophysiologic, neurochemical, pharmacologic, clinical, and epidemiologic evidence can be found to suggest a connection between the locus ceruleus, the influenza virus, and the induction of a manic psychosis.
