title: Mild hypoxia affects synaptic connectivity in cultured neuronal networks.
abstract: Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity.
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; Department of Neurology, Rijnstate Hospital, Arnhem, the Netherlands. Electronic address: jhofmeijer@rijnstate.nl.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Hofmeijer
authors.affiliation: Biomedical Signals and Sytems, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands. Electronic address: A.T.B.Mulder@student.utwente.nl.
authors.forename: Alex T B
authors.initials: AT
authors.lastname: Mulder
authors.affiliation: Biomedical Signals and Sytems, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands. Electronic address: Catarina.farinha@gmail.com.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Farinha
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; Department of Clinical Neurophysiology, Medisch Spectrum Twente, The Netherlands. Electronic address: M.J.A.M.vanPutten@utwente.nl.
authors.forename: Michel J A M
authors.initials: MJ
authors.lastname: van Putten
authors.affiliation: Biomedical Signals and Sytems, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands. Electronic address: J.leFeber@utwente.nl.
authors.forename: Joost
authors.initials: J
authors.lastname: le Feber
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques / Q000295:instrumentation; D002478:Cells, Cultured; D004558:Electric Stimulation; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
keywords: Chronic mild ischemia; Cognitive impairment; Cultured neuronal networks; Functional connectivity; Synaptic connectivity; Synaptic failure