Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice.
Lee PeytonAlfredo OliverosMaximilian Tufvesson-AlmLilly SchwielerPhillip StarskiGöran EngbergSophie ErhardtDoo-Sup ChoiPublished in: International journal of tryptophan research : IJTR (2019)
Kynurenic acid (KYNA), a glial-derived metabolite of tryptophan metabolism, is an antagonist of the alpha 7 nicotinic acetylcholine receptor and the glycine-binding site of N-methyl-d-aspartate (NMDA) receptors. Kynurenic acid levels are increased in both the brain and cerebrospinal fluid of several psychiatric disorders including bipolar disorder, schizophrenia, and Alzheimer disease. In addition, pro-inflammatory cytokines have been found to be elevated in the blood of schizophrenic patients suggesting inflammation may play a role in psychiatric illness. As both pro-inflammatory cytokines and KYNA can be elevated in the brain by peripheral lipopolysaccharide (LPS) injection, we therefore sought to characterize the role of neuroinflammation on learning and memory using a well-described dual-LPS injection model. Mice were injected with an initial injection (0.25 mg/kg LPS, 0.50 mg/kg, or saline) of LPS and then administrated a second injection 16 hours later. Our results indicate both 0.25 and 0.50 mg/kg dual-LPS treatment increased l-kynurenine and KYNA levels in the medial pre-frontal cortex (mPFC). Mice exhibited impaired acquisition of CS+ (conditioned stimulus) Pavlovian conditioning. Notably, mice showed impairment in reference memory while working memory was normal in an 8-arm maze. Taken together, our findings suggest that neuroinflammation induced by peripheral LPS administration contributes to cognitive dysfunction.
Keyphrases
- inflammatory response
- working memory
- anti inflammatory
- bipolar disorder
- lps induced
- lipopolysaccharide induced
- high fat diet induced
- traumatic brain injury
- toll like receptor
- ultrasound guided
- cerebrospinal fluid
- end stage renal disease
- major depressive disorder
- attention deficit hyperactivity disorder
- transcranial direct current stimulation
- type diabetes
- ejection fraction
- white matter
- newly diagnosed
- cognitive impairment
- wild type
- metabolic syndrome
- peritoneal dialysis
- skeletal muscle
- spinal cord injury
- blood brain barrier
- patient reported
- replacement therapy