title: Synaptic plasticity in area CA1 of rat hippocampal slices following intraventricular application of albumin.
abstract: Epileptogenesis following insults to the brain may be triggered by a dysfunctional blood-brain barrier (BBB) associated with albumin extravasation and activation of astrocytes. Using ex vivo recordings from the BBB-disrupted hippocampus after neocortical photothrombotic stroke, we previously demonstrated abnormal activity-dependent accumulation of extracellular potassium with facilitated generation of seizure like events and spreading depolarizations. Similar changes could be observed after intracerebroventricular (icv) application of albumin. We hypothesized that alterations in extracellular potassium and glutamate homeostasis might lead to alterations in synaptic interactions. We therefore assessed the effects of icv albumin on homo- and heterosynaptic plasticity in hippocampal CA1, 24h after a single injection or 7days after continuous infusion of icv albumin. We demonstrate alterations in both homo- and heterosynaptic plasticity compared to control conditions in ex vivo slice studies. Albumin-treated tissue reveals (1) reduced long-term depression following low-frequency stimulation; (2) increased long-term potentiation of population spikes in response to 20Hz stimulation; (3) potentiated responses to Schaffer collateral stimulation following high-frequency stimulation of the direct cortical input and low-frequency stimulation of alveus and finally, (4) TGFβ receptor II (TGFβR-II) involvement in albumin-induced homosynaptic plasticity changes. We conclude that albumin-induced network hyperexcitability is associated with abnormal homo- and heterosynaptic plasticity that could partly be reversed by interference with TGFβR-II-mediated signaling and therefore it might be an important factor in the process of epileptogenesis.
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany.
authors.forename: Seda
authors.initials: S
authors.lastname: Salar
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Lapilover
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Müller
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany.
authors.forename: Jan-Oliver
authors.initials: JO
authors.lastname: Hollnagel
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lippmann
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany; Departments of Cognitive and Brain Sciences, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.affiliation: Neuroscience Research Center and Institute of Neurophysiology, Charite-University Medicine Berlin, Berlin, Germany. Electronic address: uwe.heinemann@charite.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
mesh_terms: D000418:Albumins / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects*; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar
chemical_list: D000418:Albumins
keywords: Albumin; Blood-brain barrier; Epilepsy; Hippocampus; Hyperexcitability; Synaptic plasticity