Abstract
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.
Highlights
Septicemia induced by gram-negative bacteria is life threatening and can trigger a whole-body immune response which can further pathological conditions with elevated levels of released cytokines
Therapeutic treatments of bacterial septicemia vary depending on many conditions of the infection and health status of the person or animal [1]
Considering that multi-organ dysfunction can occur with septicemia, the normal excretion of prescribed pharmacological compounds can be altered, altering the levels within the body
Summary
Septicemia induced by gram-negative bacteria is life threatening and can trigger a whole-body immune response which can further pathological conditions with elevated levels of released cytokines.Therapeutic treatments of bacterial septicemia vary depending on many conditions of the infection and health status of the person or animal [1]. Septicemia induced by gram-negative bacteria is life threatening and can trigger a whole-body immune response which can further pathological conditions with elevated levels of released cytokines. There is a heavy focus on reducing the effects of the cytokines on target tissue [2,3]. Along with attempting to target receptors for LPS, there are many therapeutic approaches to reducing the immune responses [1]. One can approach this task from a whole animal or a cellular level using various animal models. Microglia in the nervous system are major contributors to secondary cytokine release. Findings suggest antidepressants such as serotonin reuptake inhibitors (SSRIs: fluoxetine, sertraline etc.) show some therapeutic effectiveness in anti-inflammatory properties on microglia [4]. It is known that LPS modifies cellular membrane potential and synaptic transmission, [5] as well as many types of therapeutics either directly or indirectly
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