40. Peripheral administration of d-cycloserine, but not norepinephrine, restores appropriate cognitive function following systemic bacterial endotoxin exposure
| Autor: | Dinko Kranjac, Brent Womble, Gary W. Boehm, M.S. Weintraub, Kyle M. Koster, Michael J. Chumley, Brenton G. Cooper, Micah J. Eimerbrink |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Endocrine and Autonomic Systems Chemistry musculoskeletal neural and ocular physiology Dentate gyrus Immunology Cycloserine Glutamate receptor Long-term potentiation AMPA receptor Hippocampal formation Behavioral Neuroscience Endocrinology nervous system Internal medicine medicine NMDA receptor Ionotropic effect medicine.drug |
| Zdroj: | Brain, Behavior, and Immunity. 32:e12 |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2013.07.052 |
| Popis: | Evidence indicates that the ionotropic NMDA and AMPA glutamate neurotransmitter receptors are critically involved in hippocampus-dependent learning and memory processes. Other reports indicate that inflammation attenuates NMDA-dependent LTP, leads to diminished hippocampal NMDAR NR1 subunit and hippocampal BDNF mRNA expression, and results in a decrease in the number of NMDARs within the dentate gyrus. Administration of the NMDA partial agonist d -cycloserine facilitates a faster recovery of recognition memory function and reinstates traumatic brain injury-induced reduction of BDNF in the CA1 subregion of the hippocampus. Affecting a different glutamate receptor, administration of exogenous IL-1beta also down-regulates the surface expression and Ser831 phosphorylation of the AMPAR GluR1. Further, this effect is abrogated via blockade of IL-1R by either anti-IL-1beta antibody or IL-1ra. Norepinephrine, binding beta-adrenergic receptors and subsequently activating the PKA and CaMKII pathways, induces transient phosphorylation of Ser831 sites of the GluR1 subunit containing AMPARs. Therefore, for the current studies, we administered peripheral d -cycloserine, or norepinephrine, to explore potential NMDAR/glycineB-, or AMPAR-mediated restoration of hippocampus-dependent fear conditioning processes following systemic LPS exposure. The results thus far indicate that peripheral administration of d -cycloserine, but not norepinephrine, restores appropriate cognitive function following systemic bacterial endotoxin exposure, though d -cycloserine administration failed to restore hippocampal BDNF expression levels diminished following LPS exposure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect