Systemic inflammation is associated with a reduction in Synaptopodin expression in the mouse hippocampus.
Systemic inflammation is known to affect memory function through the activation of immune cells and the release of inflammatory cytokines. However, the neuronal targets by which inflammatory signaling pathways affect synaptic plasticity remain not well understood. Here, we addressed the question of whether systemic lipopolysaccharide (LPS)-induced inflammation influences the expression of Synaptopodin (SP). SP is an actin-binding protein, which is considered to control the ability of neurons to express synaptic plasticity by regulating the actin-cytoskeleton and/or intracellular Ca(2+) stores. This makes SP an interesting target molecule in the context of inflammation-induced alterations in synaptic plasticity. Using quantitative PCR (qPCR)-analysis and immunohistochemistry we here demonstrate that intraperitoneal LPS-injection in two-month old male Balb/c mice leads to a reduction in hippocampal SP-levels (area CA1; 24h after injection). These changes are accompanied by a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses, similar to what is observed in SP-deficient mice. We therefore propose that systemic inflammation could exert its effects on neural plasticity, at least in part, through the down-regulation of SP in vivo.
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, 60590 Frankfurt, Germany; Cluster of Excellence Macromolecular Complexes, Goethe-University Frankfurt, 60438 Frankfurt, Germany; Department of Neurology and Sagol Center for Neurosciences, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 52621 Tel Aviv, Israel.
Andreas
A
Strehl
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Maximilian
M
Lenz
Department of Neurology and Sagol Center for Neurosciences, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 52621 Tel Aviv, Israel.
Zeev
Z
Itsekson-Hayosh
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Denise
D
Becker
Department of Neurology and Sagol Center for Neurosciences, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 52621 Tel Aviv, Israel.
Joab
J
Chapman
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Thomas
T
Deller
Department of Neurology and Sagol Center for Neurosciences, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 52621 Tel Aviv, Israel; Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, 52621 Tel HaShomer, Israel. Electronic address: nicola.maggio@sheba.health.gov.il.
Nicola
N
Maggio
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address: a.vlachos@med.uni-frankfurt.de.
Andreas
A
Vlachos
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016207:Cytokines; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D012333:RNA, Messenger; C503968:Synpo protein, mouse
Hebbian plasticity; Neuroinflammation; Spine apparatus; Tumor necrosis factor alpha; rTMS