Interleukin-6 inhibits long-term potentiation in rat hippocampal slices

Li, Ai Jun; Katafuchi, Toshihiko; Oda, Shinichiro; Hori, Tetsuro; Osuga, Yutaka

doi:10.1016/s0006-8993(96)01283-8

Cited by 131 publications

(87 citation statements)

References 37 publications

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“…For example, LIF mRNA is increased more than tenfold 4 h after electrode insertion in the hippocampus, a response similar to the upregulation seen after scalpel-induced injury to the cortex (Banner et al 1997). Importantly, several of the factors we found upregulated by electrode insertion (including IL-1␤, IL-6, and BDNF) are able to alter synaptic properties when exogenously applied to hippocampal preparations (Katsuki et al 1990;Bellinger et al 1993;Kang and Schuman 1995;Cunningham et al 1996;Li et al 1997;Schneider et al 1998).…”

Section: Jankowsky Et Alsupporting

confidence: 66%

“…While one of these, BDNF, had been previously studied, expression of the cytokine IL-6 had not yet been examined in this context. Because exogenous application of IL-6 can affect synaptic properties (Li et al 1997), upregulation of this cytokine by synaptic activity, combined with its restricted spatial pattern of expression, suggests an interesting way in which local synaptic plasticity may be regulated, as discussed in more detail below. Identification of these two factors required that we employ one of the most technically challenging preparations for studying hippocampal LTP, using electrodes that are chronically implanted into the Schaffer collateral pathway in order to separate the effects of stimulation from the injury associated with electrode insertion.…”

Section: Cytokine Responses To Hippocampal Electrophysiologymentioning

confidence: 99%

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Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques

Jankowsky¹,

Derrick²,

Patterson³

2000

Learn. Mem.

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Because exogenous application of a number of cytokines and growth factors can alter synaptic properties, we sought to determine if endogenous cytokine expression is affected by neuronal activity. In addition, we examined whether cytokine expression is altered by the techniques used to stimulate and record from hippocampal neurons. Using semi-quantitative RNase protection and RT-PCR assays, we studied the expression of 18 cytokine, growth factor, and receptor genes in the hippocampus following the induction of Schaffer collateral-CA1 long-term potentiation (LTP). We found that various cytokines are dramatically induced following preparation of slices for in vitro recording and as a result of injury following acute electrode placement in vivo. These increases can be overcome in vivo, however, using permanent electrodes implanted three weeks prior to testing. Using this chronic preparation, we found that interleukin-6 (IL-6) mRNA was upregulated nearly 20-fold by LTP induction in vivo, marking the first demonstration of endogenous regulation of this cytokine in response to LTP. In situ hybridization for IL-6 revealed that upregulation is tightly localized near the site of stimulation and is detected only in non-neuronal cells, identified as GFAP+ astrocytes and GFAP− cells within proximal blood vessels. Coupled with previous results showing that exogenously applied IL-6 can prevent the induction of LTP, this finding suggests a mechanism by which the local release of a cytokine could regulate LTP at nearby sites.

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Section: Jankowsky Et Alsupporting

confidence: 66%

Section: Cytokine Responses To Hippocampal Electrophysiologymentioning

confidence: 99%

Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques

Jankowsky¹,

Derrick²,

Patterson³

2000

Learn. Mem.

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“…Immune activity stimulated by HSV infection in the central nervous system has been observed [36][37][38] and many immune messengers have the ability to affect hippocampal physiology. [39][40][41][42][43][44][45] While measures of immune activity were not taken, the current data support the idea that vector delivery does not stimulate an immune response sufficient to alter hippocampal synaptic physiology.…”

Section: Figure 3 Panels Show Expression Patterns In Representative Asupporting

confidence: 54%

Delivery of herpes simplex virus amplicon-based vectors to the dentate gyrus does not alter hippocampal synaptic transmission in vivo

Dumas

McLaughlin

et al. 1999

Gene Ther

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Herpes simplex virus type-1 (HSV) amplicon vectors con-(I/O) curves were not altered by infection. Paired-pulse taining neuroprotective genes can alter cell physiology and facilitation at either recording site was also unaffected. Xenhance survival following various insults. However, to gal-positive granule cells surrounded the recording elecdate, little is known about effects of viral infection itself trode (PP-DG recording) and stimulating electrode tracts (independent of the gene delivered) on neuronal physi-(MF-CA3 recording) in animals that received vector, sugology. Electrically-evoked synaptic responses are routinely gesting that we had measured function, at least in part, in recorded to measure functional alterations in the nervous infected neurons. Because of the negative electrophysiolsystem and were used here to assess the potential capaogical result, we sought to deliver a gene with an HSV bility of HSV vectors to disrupt physiology of the hippocamamplicon which would affect the measured endpoints, as pus (a forebrain structure involved in learning that is highly a positive control. Delivery of calbindin D 28k potentiated susceptible to necrotic insult, making it a frequent target in PP-DG synaptic strength, indicating that our recording sysgene therapy research). Population excitatory post-synaptem could detect alterations due to vector expression. tic potentials (EPSPs) were recorded in the dentate gyrus Thus, the data indicate that HSV vectors are benign, in (DG) and in area CA3 in vivo 72 h after infusion of an HSV regard to effects on synaptic function, and support the use vector expressing a reporter gene (lacZ) or vehicle into the of these vectors as a safe method to deliver selected DG. Evoked perforant path (PP-DG) or mossy fiber (MFgenes to the central nervous system. CA3) EPSPs slope values measured across input/output

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“…Thus, IL-1 induces the synthesis of IL-6 and TNF-␣ in astrocytes and microglia (Bartfai and Schultzberg, 1993;Schobitz et al, 1994), and many actions of IL-1 in CNS are mediated by these cytokines (Rothwell, 1991). IL-6 and TNF-␣, in turn, have been reported to affect synaptic transmission (Tancredi et al, 1992;Schobitz et al, 1994;Li et al, 1997), and mice overexpressing IL-6 and TNF in glia develop both seizures and neurodegeneration (Campbell et al, 1993;Akassoglou et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β Immunoreactivity and Microglia Are Enhanced in the Rat Hippocampus by Focal Kainate Application: Functional Evidence for Enhancement of Electrographic Seizures

et al. 1999

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Using immunocytochemistry and ELISA, we investigated the production of interleukin (IL)-1␤ in the rat hippocampus after focal application of kainic acid inducing electroencephalographic (EEG) seizures and CA3 neuronal cell loss. Next, we studied whether EEG seizures per se induced IL-1␤ and microglia changes in the hippocampus using bicuculline as a nonexcitotoxic convulsant agent. Finally, to address the functional role of this cytokine, we measured the effect of human recombinant (hr)IL-1␤ on seizure activity as one marker of the response to kainate.Three and 24 hr after unilateral intrahippocampal application of 0.19 nmol of kainate, IL-1␤ immunoreactivity was enhanced in glia in the injected and the contralateral hippocampi. At 24 hr, IL-1␤ concentration increased by 16-fold ( p Ͻ 0.01) in the injected hippocampus. Reactive microglia was enhanced with a pattern similar to IL-1␤ immunoreactivity. Intrahippocampal application of 0.77 nmol of bicuculline methiodide, which induces EEG seizures but not cell loss, enhanced IL-1␤ immunoreactivity and microglia, although to a less extent and for a shorter time compared with kainate. One nanogram of (hr)IL-1␤ intrahippocampally injected 10 min before kainate enhanced by 226% the time spent in seizures ( p Ͻ 0.01). This effect was blocked by coinjection of 1 g (hr)IL-1␤ receptor antagonist or 0.1 ng of 3-((ϩ)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate, selective antagonists of IL-1␤ and NMDA receptors, respectively.Thus, convulsant and/or excitotoxic stimuli increase the production of IL-1␤ in microglia-like cells in the hippocampus. In addition, exogenous application of IL-1␤ prolongs kainateinduced hippocampal EEG seizures by enhancing glutamatergic neurotransmission.

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Interleukin-6 inhibits long-term potentiation in rat hippocampal slices

Cited by 131 publications

References 37 publications

Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques

Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques

Delivery of herpes simplex virus amplicon-based vectors to the dentate gyrus does not alter hippocampal synaptic transmission in vivo

Interleukin-1β Immunoreactivity and Microglia Are Enhanced in the Rat Hippocampus by Focal Kainate Application: Functional Evidence for Enhancement of Electrographic Seizures

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