title: Neuroinflammation-Induced Memory Deficits Are Amenable to Treatment with D-Cycloserine.
abstract: Cognitive deficits, especially memory loss, are common following many types of brain insults which are associated with neuroinflammation, although the underlying mechanisms are not entirely clear. The present study aimed to characterize the long-term cognitive and behavioral impairments in a mouse model of neuroinflammation in the absence of other insults and to evaluate the therapeutic potential of D-cycloserine (DCS). DCS is a co-agonist of the NMDA receptor that ameliorates cognitive deficits in models of TBI and stroke. Using a mouse model of global neuroinflammation induced by intracisternal (i.c.) administration of endotoxin (LPS), we found long-lasting microgliosis, memory deficits, impaired LTP, and reduced levels of the obligatory NR1 subunit of the NMDA receptor. A single administration of DCS, 1 day after i.c. LPS reduced microgliosis, reversed the cognitive deficits and restored LTP and NR1 levels. These results demonstrate that neuroinflammation alone, in the absence of trauma or ischemia, can cause persistent (>6 months) memory deficits linked to deranged NNMDA receptor function and suggest a possible role for NMDA co-agonists in reducing the cognitive sequelae of neuroinflammation.
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat Gan, Israel. s.lirazaltsman@gmail.com.|Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem, Israel. s.lirazaltsman@gmail.com.
authors.forename: Sigal
authors.initials: S
authors.lastname: Liraz-Zaltsman
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem, Israel.
authors.forename: Rami
authors.initials: R
authors.lastname: Yaka
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem, Israel.
authors.forename: Dalia
authors.initials: D
authors.lastname: Shabashov
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
authors.affiliation: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat Gan, Israel.|Department of Neurology, Stony Brook University School of Medicine, Stony Brook, New York, USA.
authors.forename: Anat
authors.initials: A
authors.lastname: Biegon
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003523:Cycloserine / Q000494:pharmacology / Q000627:therapeutic use*; D005911:Gliosis; D008070:Lipopolysaccharides / Q000633:toxicity; D017774:Long-Term Potentiation; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine
keywords: Cognitive deficits; DCS; Endotoxin; LPS; NMDA receptors; Neuroinflammation