The endotoxic effect from gram negative bacteria is primarily due to the lipopolysaccharides (LPS). LPS activates the innate immune response through a Toll‐like receptor 4 (TLR4) known as the CD14/TLR4/MD2 receptor complex in mammals. The Toll receptors are conserved from primates to insects. However, in insects the peptidoglycan recognition proteins (PGRPs) are the receptors which respond to LPS from gram negative bacteria. These PGRPs activate the Immune Deficient (IMD) signaling cascade. There is a family of these receptors known in Drosophila melanogaster but their expression profiles in different tissues has yet to be fully elucidated. We examined a variety of model preparations to better understand the acute actions of exposure to LPS of Serratia marcescens to better understand the varied mechanisms of action. There is a differential, dose dependent effect of LPS in increasing and decreasing HR heart rate (HR) in the larval medicinal blow fly (Phaenicia sericata) and a fruit fly (Drosophila melanogaster). LPS depressed evoked and miniature (quantal) EJPs while hyperpolarizing the skeletal muscle in larval Drosophila, but increased EJPs with no effect on muscle membrane potential at the crayfish NMJ. Both NMJs are glutamatergic. LPS had no effect on sensory transduction of proprioceptive sensory neurons in crayfish and blue crab. LPS at the cholinergic frog NMJ depressed synaptic transmission with no effect on muscle membrane potential. LPS depressed sensory‐CNS‐motor nerve circuits in both crayfish and larval Drosophila. Synaptically‐evoked population spikes in field CA1 of the mouse hippocampus were also significantly reduced by acute LPS applications. The varied effects of LPS in different model systems paves the way to examining differential cellular mechanisms induced by acute exposure to LPS. Support or Funding Information Dept of Biology, Univ. of KY laboratory funds and personal funds (RLC) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The effect of bacterial sepsis on animal behavior and physiology is complex due to direct and indirect actions. The most common form of bacterial sepsis in humans is from gram-negative bacterial strains. The endotoxin (lipopolysaccharide, LPS) and/or associated peptidoglycans from the bacteria are the key agents to induce an immune response, which then produces a cascade of immunological consequences. However, there are direct actions of LPS and associated peptidoglycans on cells which are commonly overlooked. This study showed behavioral and neural changes in larval Drosophila fed commercially obtained LPS from Serratia marcescens. Locomotor behavior was not altered, but feeding behavior increased and responses to sensory tactile stimuli were decreased. In driving a sensory-central nervous system (CNS)-motor neural circuit in in-situ preparations, direct application of commercially obtained LPS initially increased evoked activity and then decreased and even stopped evoked responses in a dose-dependent manner. With acute LPS and associated peptidoglycans exposure (10 min), the depressed neural responses recovered within a few minutes after removal of LPS. Commercially obtained LPS induces a transitory hyperpolarization of the body wall muscles within seconds of exposure and alters activity within the CNS circuit. Thus, LPS and/or associated peptidoglycans have direct effects on body wall muscle without a secondary immune response.

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The release of the endotoxin lipopolysaccharides (LPS) from gram-negative bacteria is key in the induction of the downstream cytokine release from cells targeting cells throughout the body. However, LPS itself has direct effects on cellular activity and can alter synaptic transmission. Animals experiencing septicemia are generally in a critical state and are often treated with various pharmacological agents. Since antidepressants related to the serotonergic system have been shown to have a positive outcome for septicemic conditions impacting the central nervous system, the actions of serotonin (5-HT) on neurons also exposed to LPS were investigated. At the model glutamatergic synapse of the crayfish neuromuscular junction (NMJ), 5-HT primarily acts through a 5-HT2A receptor subtype to enhance transmission to the motor neurons. LPS from Serratia marcescens also enhances transmission at the crayfish NMJ but by a currently unknown mechanism. LPS at 100 µg/mL had no significant effect on transmission or on altering the response to 5-HT. LPS at 500 µg/mL increased the amplitude of the evoked synaptic excitatory junction potential, and 5-HT in combination with 500 µg/mL LPS continued to promote enhanced transmission. The preparations maintained responsiveness to serotonin in the presence of low or high concentrations of LPS.