Interleukin-10 Facilitates Glutamatergic Synaptic Transmission and Homeostatic Plasticity in Cultured Hippocampal Neurons

Nenov, Miroslav N.; Konakov, M. V.; Teplov, Ilia; Levin, S. G.

doi:10.3390/ijms20133375

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…IL‐10 levels (pg/mL) were significantly lower in LPS + α‐synO‐treated mice (9.29 ± 1.17: n = 5; ** P < 0.01 and **** P < 0.0001, Tukey’s test) compared to Veh + Veh‐, LPS + Veh‐ and Veh + α‐synO‐treated animals (18.38 ± 2.03,17.71 ± 1.52 and 23.52 ± 1.33; 6/group). IL‐6 and IL‐10 are linked to cognitive deficits [46,47], with opposite effects on LTP [48–50]. Moreover, high levels of IL‐6 correlate with the severity of PD cognitive deficits [51].…”

Section: Resultsmentioning

confidence: 99%

Peripheral inflammation exacerbates α‐synuclein toxicity and neuropathology in Parkinson's models

Vitola

Balducci

Baroni

et al. 2020

Neuropathology Appl Neurobio

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Aims Parkinson’s disease and related disorders are devastating neurodegenerative pathologies. Since α‐synuclein was identified as a main component of Lewy bodies and neurites, efforts have been made to clarify the pathogenic mechanisms of α‐synuclein's detrimental effects. α‐synuclein oligomers are the most harmful species and may recruit and activate glial cells. Inflammation is emerging as a bridge between genetic susceptibility and environmental factors co‐fostering Parkinson’s disease. However, direct evidence linking inflammation to the harmful activities of α‐synuclein oligomers or to the Parkinson’s disease behavioural phenotype is lacking. Methods To clarify whether neuroinflammation influences Parkinson’s disease pathogenesis, we developed: (i) a ‘double‐hit’ approach in C57BL/6 naive mice where peripherally administered lipopolysaccharides were followed by intracerebroventricular injection of an inactive oligomer dose; (ii) a transgenic ‘double‐hit’ model where lipopolysaccharides were given to A53T α‐synuclein transgenic Parkinson’s disease mice. Results Lipopolysaccharides induced a long‐lasting neuroinflammatory response which facilitated the detrimental cognitive activities of oligomers. LPS‐activated microglia and astrocytes responded differently to the oligomers with microglia activating further and acquiring a pro‐inflammatory M1 phenotype, while astrocytes atrophied. In the transgenic ‘double‐hit’ A53T mouse model, lipopolysaccharides aggravated cognitive deficits and increased microgliosis. Again, astrocytes responded differently to the double challenge. These findings indicate that peripherally induced neuroinflammation potentiates the α‐synuclein oligomer’s actions and aggravates cognitive deficits in A53T mice. Conclusions The fine management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some behavioural aspects in α‐synucleinopathies.

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Section: Resultsmentioning

confidence: 99%

Peripheral inflammation exacerbates α‐synuclein toxicity and neuropathology in Parkinson's models

Vitola

Balducci

Baroni

et al. 2020

Neuropathology Appl Neurobio

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“…However, activation of GLP‐1 receptors was previously reported to enhance the depolarization‐evoked release of glutamate and GABA in the mouse cortex and hippocampus. 62 , 63 …”

Section: Discussionmentioning

confidence: 99%

Spinal microglial β‐endorphin signaling mediates IL‐10 and exenatide‐induced inhibition of synaptic plasticity in neuropathic pain

Peng

Wei

et al. 2021

CNS Neurosci Ther

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“…Further, IL10 expression has been reported for cultured microglia ( 63 ). Notably, IL10 has recently been linked to the modulation of excitatory neurotransmission ( 64 , 65 ), suggesting that microglia may affect synaptic plasticity via IL10. However, to date, transcriptome analyses of microglia isolated from various in vivo disease models have failed to demonstrate IL10 expression in microglia ( 28 , 66 – 68 ).…”

Section: Discussionmentioning

confidence: 99%

Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation

et al. 2020

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Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

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Interleukin-10 Facilitates Glutamatergic Synaptic Transmission and Homeostatic Plasticity in Cultured Hippocampal Neurons

Cited by 21 publications

References 35 publications

Peripheral inflammation exacerbates α‐synuclein toxicity and neuropathology in Parkinson's models

Peripheral inflammation exacerbates α‐synuclein toxicity and neuropathology in Parkinson's models

Spinal microglial β‐endorphin signaling mediates IL‐10 and exenatide‐induced inhibition of synaptic plasticity in neuropathic pain

Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation

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