scholarly journals Microglia-dependent presynaptic disruption in an organotypic hippocampal slice culture model of neuroinflammation

2018 ◽  
Author(s):  
Olivia Sheppard ◽  
Michael P Coleman ◽  
Claire S Durrant
Keyword(s):  
Culture Medium ◽  
Molecular Mechanisms ◽  
Hippocampal Slice ◽  
Synaptic Proteins ◽  
Slice Culture ◽  
Partial Recovery ◽  
Wild Type ◽  
Aseptic Inflammation ◽  
Operative Trauma ◽  
Hippocampal Slice Culture

Background: Systemic inflammation, such as occurs during sepsis, bone fracture, infections or post-operative trauma, has been linked to synapse loss and cognitive decline in human patients and animal models. Organotypic hippocampal slice cultures (OHSCs) represent an underused tool in neuroinflammation; retaining much of the neuronal architecture, synaptic connections and diversity of cell types present in the hippocampus in vivo whilst providing convenient access to manipulate and sample the culture medium and observe cellular reactions as in other in vitro methods. Here we report the development of an OHSC model of synaptic disruption after aseptic inflammation and investigate the underlying mechanism. Methods: OHSCs were generated from P6-P9 C57BL/6, the APP transgenic TgCRND8 model, or wild-type littermate mice according to the interface method. Aseptic inflammation was induced via addition of lipopolysaccharide (LPS) and cultures were analysed for changes in synaptic proteins via western blot. qPCR and ELISA analysis of the slice tissue and culture medium respectively determined changes in gene expression and protein secretion. Microglia were selectively depleted using the toxin clodronate and the effect of IL1β was assessed using a specific neutralising monoclonal antibody. Results: Addition of LPS caused a loss of the presynaptic protein synaptophysin via a mechanism dependent on microglia and involving IL1β. Washout of LPS via medium exchange allows for partial recovery of synaptic protein levels after 2 weeks. TgCRND8 OHSCs do not show alterations in IL1β expression at a timepoint where they exhibit spontaneous synaptophysin loss, and LPS does not alter levels of APP or Aβ in wild-type OHSCs. This indicates that although synaptophysin loss is seen in both systems, there is likely to be distinct underlying pathogenic mechanisms between the neuroinflammatory and amyloid models. Conclusions: We report the development of an OHSC model of LPS-induced synaptophysin loss and demonstrate a key role for microglia and involvement of IL1β. We propose that distinct molecular mechanisms lead to synaptophysin protein loss in LPS- exposed versus TgCRND8 OHSCs and provide a new experimental paradigm for assessing chronic changes in synaptic proteins, and synaptic plasticity, following acute inflammatory insults.

scholarly journals In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simone Nardin Weis ◽  
Jaques Miranda F. Souza ◽  
Juliana Bender Hoppe ◽  
Marina Firmino ◽  
Manfred Auer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hippocampal Slice ◽  
Neurological Diseases ◽  
Hippocampal Slices ◽  
Glycogen Metabolism ◽  
Pentose Phosphate ◽  
Slice Culture ◽  
Organotypic Hippocampal Slice Culture ◽  
Hippocampal Slice Culture

AbstractSex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.

Neuroprotective effects of FK506 against excitotoxicity in organotypic hippocampal slice culture

2010 ◽  
Vol 474 (3) ◽  
pp. 126-130 ◽  
Author(s):  
Kyung Hee Lee ◽  
Ran Won ◽  
Un Jeng Kim ◽  
Ga Min Kim ◽  
Myung-Ae Chung ◽  
...  
Keyword(s):  
Hippocampal Slice ◽  
Slice Culture ◽  
Neuroprotective Effects ◽  
Organotypic Hippocampal Slice Culture ◽  
Hippocampal Slice Culture

scholarly journals ESP-102, a Combined Herbal Extract ofAngelica gigas,Saururus chinensis, andSchisandra chinensis, Changes Synaptic Plasticity and Attenuates Scopolamine-Induced Memory Impairment in Rat Hippocampus Tissue

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hyun-Bum Kim ◽  
Eun-Sang Hwang ◽  
Ga-Young Choi ◽  
Seok Lee ◽  
Tae-Suk Park ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Slice ◽  
Neuroprotective Effect ◽  
Long Term Potentiation ◽  
Herbal Extract ◽  
Excitatory Postsynaptic Potential ◽  
Slice Culture ◽  
Neuroprotective Effects ◽  
Hippocampal Slice Culture ◽  
Saururus Chinensis

ESP-102, an extract fromAngelica gigas, Saururus chinensis, andSchisandra chinensis, has been used as herbal medicine and dietary supplement in Korea. Despite the numerous bioactivitiesin vitroandin vivostudies, its effects on neuronal networks remain elusive. To address the neuronal effect, we examined synaptic plasticity in organotypic hippocampal slice culture with multielectrode array. Our results showed an increase in excitatory postsynaptic potential (EPSP), indicating the induction of long-term potentiation (LTP), in the presence of ESP-102. In addition, the neuroprotective effect of ESP-102 was also tested by application of scopolamine to the hippocampal slice. Interestingly, ESP-102 competitively antagonized the preventative LTP effect induced by scopolamine. The scopolamine-induced reduction in brain-derived neurotrophic factor (BDNF) and GluR-2 expression was also rescued by ESP-102. In terms of mode of action, ESP-102 appears to act on the presynaptic region independent of AMPA/NMDA receptors. Based on these findings, ESP-102 can be suggested as a novel herbal ingredient with memory enhancing as well as neuroprotective effects.

Effects of sugars and polyols on basidiocarp formation in a phosphoglucose isomerase mutant of Coprinus cinereus

1984 ◽  
Vol 30 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Hiroshi Nyunoya ◽  
Tsuneo Takemaru ◽  
Tatsuo Ishikawa
Keyword(s):  
Culture Medium ◽  
Complete Recovery ◽  
Biochemical Properties ◽  
Phosphoglucose Isomerase ◽  
Coprinus Cinereus ◽  
Partial Recovery ◽  
Wild Type ◽  
In The Wild ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Basidiocarp Formation

Several biochemical properties of a mutant deficient in phosphoglucose isomerase (pgi) of Coprinus cinereus were examined in connection with its ability to produce basidiocarps. Mycelium of the pgi mutant accumulated glucose-6-phosphate and showed higher glucose-6-phosphate dehydrogenase activity than wild type. A conventional fruiting medium did not support basidiocarp formation by the homozygous dikaryon pgi/pgi, but the addition of a reduced amount of glucose plus a compensatory amount of fructose to the culture medium resulted in partial recovery of fruiting ability. This modification of the culture medium decreased the intracellular glucose-6-phosphate to almost the same level as in the wild type. The addition of polyols such as mannitol resulted in complete recovery of fruiting ability by the dikaryon pgi/pgi without affecting the level of glucose-6-phosphate. Mycelium of the mutant showed an elevated activity of NAD-linked polyol dehydrogenase and an elevated intracellular NAD level, irrespective of whether the mycelium was grown in the presence or absence of polyol.

Development of mossy fiber synapses in hippocampal slice culture

1994 ◽  
Vol 80 (1-2) ◽  
pp. 244-250 ◽  
Author(s):  
O. Robain ◽  
G. Barbin ◽  
Th. Billette de Villemeur ◽  
L. Jardin ◽  
Th. Jahchan ◽  
...  
Keyword(s):  
Hippocampal Slice ◽  
Mossy Fiber ◽  
Slice Culture ◽  
Hippocampal Slice Culture

P4-169: β-amyloid neurotoxicity in organotypic hippocampal slice culture is attenuated by melatonin: involvement of GSK-3β, tau and neuroinflammation

2009 ◽  
Vol 5 (4S_Part_16) ◽  
pp. P481-P481
Author(s):  
Christianne Salbego ◽  
Juliana B. Hoppe ◽  
Rudimar L. Frozza ◽  
Ana Paula Horn ◽  
Ricardo A. Comiran ◽  
...  
Keyword(s):  
Hippocampal Slice ◽  
Slice Culture ◽  
Organotypic Hippocampal Slice Culture ◽  
Hippocampal Slice Culture ◽  
Β Amyloid ◽  
Gsk 3Β
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