Interleukin-10 restores glutamate receptor-mediated Ca<sup>2+</sup>-signaling in brain circuits under loss of <i>Sip1</i> transcription factor

Turovskaya, M. V.; Epifanova, Ekaterina A.; Tarabykin, Victor; Бабаев, А.А.; Turovsky, Egor A.

doi:10.1080/00207454.2020.1803305

Cited by 11 publications

(10 citation statements)

References 58 publications

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“…Since the inhibitory gliotransmitters release, e.g., D-serine from the astrocytes, which depends on Ca 2+ elevation [49], we hypothesize that reduced intracellular Ca 2+ levels lead to a failure in the control of neuronal activity and increased SRs and BRs. Corroborating our hypothesis, a reduction in neuronal [Ca 2+ ] i transients, and a relative abnormal neurotransmission, was also noticed in acute models of epileptiform activity in vitro on Sip1 deficient mice [50], and in ischemia-like conditions in hippocampal neurons and astrocytes during oxygen-glucose deprivation/reoxygenation [51]. We noticed that increasing the number of astrocytes, and therefore most probably the amount of GABA A Rs, increased the time needed for the drug to block most of these receptors.…”

Section: Discussionsupporting

confidence: 83%

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Ahtiainen

Genocchi

Tanskanen

et al. 2021

IJMS

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Astrocytes and neurons respond to each other by releasing transmitters, such as γ-aminobutyric acid (GABA) and glutamate, that modulate the synaptic transmission and electrochemical behavior of both cell types. Astrocytes also maintain neuronal homeostasis by clearing neurotransmitters from the extracellular space. These astrocytic actions are altered in diseases involving malfunction of neurons, e.g., in epilepsy, Alzheimer’s disease, and Parkinson’s disease. Convulsant drugs such as 4-aminopyridine (4-AP) and gabazine are commonly used to study epilepsy in vitro. In this study, we aim to assess the modulatory roles of astrocytes during epileptic-like conditions and in compensating drug-elicited hyperactivity. We plated rat cortical neurons and astrocytes with different ratios on microelectrode arrays, induced seizures with 4-AP and gabazine, and recorded the evoked neuronal activity. Our results indicated that astrocytes effectively counteracted the effect of 4-AP during stimulation. Gabazine, instead, induced neuronal hyperactivity and synchronicity in all cultures. Furthermore, our results showed that the response time to the drugs increased with an increasing number of astrocytes in the co-cultures. To the best of our knowledge, our study is the first that shows the critical modulatory role of astrocytes in 4-AP and gabazine-induced discharges and highlights the importance of considering different proportions of cells in the cultures.

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Section: Discussionsupporting

confidence: 83%

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Ahtiainen

Genocchi

Tanskanen

et al. 2021

IJMS

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“…Besides this, there are increasing amounts of studies describing the role of anti-inflammatory regulators for ischemic stroke. Interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to be beneficial for neurogenesis in the ischemic brain by attenuating pro-inflammatory signals and upregulating anti-apoptotic proteins [ 67 ]. The transforming growth factor-β (TGF-β), another neuroprotective and anti-inflammatory mediator produced by astrocytes and microglia, when overexpressed, reduced ischemic brain injury in experimental studies, while brain damage was exacerbated when TGF-β was blocked [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Jak2 Inhibitor AG490 Improved Poststroke Central and Peripheral Inflammation and Metabolic Abnormalities in a Rat Model of Ischemic Stroke

et al. 2021

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Poststroke hyperglycemia and inflammation have been implicated in the pathogenesis of stroke. Janus Kinase 2 (Jak2), a catalytic signaling component for cytokine receptors such as Interleukin-6 (IL-6), has inflammatory and metabolic properties. This study aimed to investigate the roles of Jak2 in poststroke inflammation and metabolic abnormality in a rat model of permanent cerebral ischemia. Pretreatment with Jak2 inhibitor AG490 ameliorated neurological deficit, brain infarction, edema, oxidative stress, inflammation, caspase-3 activation, and Zonula Occludens-1 (ZO-1) reduction. Moreover, in injured cortical tissues, Tumor Necrosis Factor-α, IL-1β, and IL-6 levels were reduced with concurrent decreased NF-κB p65 phosphorylation, Signal Transducers and Activators of Transcription 3 phosphorylation, Ubiquitin Protein Ligase E3 Component N-Recognin 1 expression, and Matrix Metalloproteinase activity. In the in vitro study on bEnd.3 endothelial cells, AG490 diminished IL-6-induced endothelial barrier disruption by decreasing ZO-1 decline. Metabolically, administration of AG490 lowered fasting glucose, with improvements in glucose intolerance, plasma-free fatty acids, and plasma C Reactive Proteins. In conclusion, AG490 improved the inflammation and oxidative stress of neuronal, hepatic, and muscle tissues of stroke rats as well as impairing insulin signaling in the liver and skeletal muscles. Therefore, Jak2 blockades may have benefits for combating poststroke central and peripheral inflammation, and metabolic abnormalities.

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“…The metabotropic GluRs in the central nervous system mediate the postsynaptic neuronal response to glutamate, modulating both NMDAR and AMPAR activities, as well as cellular proliferation, growth, migration, survival, and calcium-mediated cellular homeostasis (Pin & Duvoisin 1995)Montpellier, were decreased in hippocampal tissues of sham mice and were increased by BHLHE40 overexpression. BHLHE40 has been reported to be a crucial repressor of IL-10 (Huynh et al 2018), and IL-10 restores glutamate receptor-controlled Ca 2 + -pathway in brain circuits (Turovskaya et al 2020). BHLHE40 can increase the expression of CXCL12 (Teng et al 2020), and CXCL12 facilitates glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus (Heinisch & Kirby 2010).…”

Section: Discussionmentioning

confidence: 99%

BHLHE40 modulates post-traumatic stress disorder behaviors with the involvement of the PI3K/AKT signaling pathway

Aji¹,

Aihemaiti²,

Zou³

et al. 2021

An. Acad. Bras. Ciênc.

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Post-traumatic stress disorder (PTSD) is closely related to the exposure to traumatic events and results in the structural and functional changes of hippocampus.Human basic helix-loop-helix family member e40 (BHLHE40) was reported to be implicated with neuron maturity and neuronal differentiation. The present study aimed to reveal the role of BHLHE40 on single-prolonged stress (SPS) model of PTSD in mice.The morris water maze test, open fi eld test and contextual fear test were conducted to assess memory defi cits, anxiety-like behaviors, and freezing of mice. Western blot was performed to identify proteins and reveal their levels in hippocampal tissues. We found that mice receiving SPS exhibited increased anxiety-like behaviors, memory defi cits, and prolonged freezing time. The protein levels of BHLHE40 were downregulated in the hippocampal tissues of SPS mice. SPS reduced the protein levels of glutamate receptors, while overexpression of BHLHE40 promoted glutamate receptor protein levels in SPS mice. Moreover, BHLHE40 overexpression activated the PI3K/AKT pathway. BHLHE40 overexpression ameliorated the SPS-induced PTSD-like behavioral defi cits. Overall, BHLHE40 promotes glutamate receptor protein levels to ameliorate PTSD-like behaviors with the involvement of the PI3K/AKT pathway. This novel discovery may provide a potential target for the improvement of PTSD.

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Interleukin-10 restores glutamate receptor-mediated Ca²⁺-signaling in brain circuits under loss of Sip1 transcription factor

Cited by 11 publications

References 58 publications

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Jak2 Inhibitor AG490 Improved Poststroke Central and Peripheral Inflammation and Metabolic Abnormalities in a Rat Model of Ischemic Stroke

BHLHE40 modulates post-traumatic stress disorder behaviors with the involvement of the PI3K/AKT signaling pathway

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Interleukin-10 restores glutamate receptor-mediated Ca2+-signaling in brain circuits under loss of Sip1 transcription factor

Cited by 11 publications

References 58 publications

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

Jak2 Inhibitor AG490 Improved Poststroke Central and Peripheral Inflammation and Metabolic Abnormalities in a Rat Model of Ischemic Stroke

BHLHE40 modulates post-traumatic stress disorder behaviors with the involvement of the PI3K/AKT signaling pathway

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Product

Resources

About

Interleukin-10 restores glutamate receptor-mediated Ca²⁺-signaling in brain circuits under loss of Sip1 transcription factor