TLR2- and TLR3-activated microglia induce different levels of neuronal network dysfunction in a context-dependent manner

Schilling, Simone; Chausse, Bruno; Dikmen, Hasan; Almouhanna, Fadi; Hollnagel, Jan‐Oliver; Lewen, Andrea; Kann, Oliver

doi:10.1016/j.bbi.2021.05.013

Cited by 33 publications

(11 citation statements)

References 94 publications

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“…As a high-frequency synchronization of neuron populations, gamma oscillations are susceptible to metabolic and oxidative stress since a quick requisition for mitochondria is necessary to meet the energy requirements imposed by neuronal activities (Kann et al, 2011). Different levels of network dysfunction are induced by TLR-activated microglia, which is primarily mediated by the excessive release of reactive oxygen and nitrogen species rather than proinflammatory cytokines (Schilling et al, 2021). In hippocampal slices in situ, IFN-gamma-activated microglia upregulate the expression of inducible nitric oxide synthase (iNOS) and subsequently produce a large amount of NO, resulting in a decrease in the frequency of gamma-band oscillations (Ta et al, 2019).…”

Section: Central Nervous System Perturbation: Inflammation and Oxidat...mentioning

confidence: 99%

The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Guan

Wang

Huang

et al. 2022

Front. Cell. Neurosci.

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Gamma oscillation is the synchronization with a frequency of 30–90 Hz of neural oscillations, which are rhythmic electric processes of neuron groups in the brain. The inhibitory interneuron network is necessary for the production of gamma oscillations, but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this network to malfunction. Gamma oscillations specifically control the connectivity between different brain regions, which is crucial for perception, movement, memory, and emotion. Studies have linked abnormal gamma oscillations to conditions of the central nervous system, including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Evidence suggests that gamma entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses the function of gamma oscillations in advanced brain activities from both a physiological and pathological standpoint, and it emphasizes gamma entrainment as a potential therapeutic approach for a range of neuropsychiatric diseases.

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Section: Central Nervous System Perturbation: Inflammation and Oxidat...mentioning

confidence: 99%

The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Guan

Wang

Huang

et al. 2022

Front. Cell. Neurosci.

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“…This loss of rhythmicity of synaptic transmission likely accounts for the degradation of the network rhythm since the generation of gamma oscillations depends on balanced excitatory and inhibitory interplay [ 12 ]. However, due to the diverse evidence of purinergic signaling in the modulation of the operational capacity of the hippocampal circuitry, and commonalities found in our study regarding gal3-induced neuronal network collapse, a possible underlying mechanism involving ATP/adenosine receptor activation deserves further research, without exclusion of an indirect involvement of astrocytes, nitric oxide, metabolic arrestment [ 31 , 32 , 102 , 108 ] and a direct effect of gal3 on PCs and FSN. Also, effects of microglial activation due to the slicing procedure appear negligible in our study since microglia seem to be less relevant for moderate tissue repair at the slice cut surfaces as well as for synaptic remodelling and neuronal network formation, at least during the second and third postnatal weeks of hippocampal maturation in situ [ 109 , 110 ].…”

Section: Discussionmentioning

confidence: 76%

Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

Arroyo-García

Bachiller

Ruiz

et al. 2023

Transl Neurodegener

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Background Alzheimer’s disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin-3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown. Methods Here, we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo (20–80 Hz) by performing electrophysiological recordings in the hippocampal CA3 area of wild-type (WT) mice and of the 5×FAD mouse model of AD. In addition, the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes, and amyloid-β (Aβ) plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout (KO). Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner, which was accompanied by impairment of cellular dynamics in fast-spiking interneurons (FSNs) and pyramidal cells. We found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139, which also prevented Aβ42-induced degradation of gamma oscillations. Furthermore, the 5×FAD mice lacking gal3 (5×FAD-Gal3KO) exhibited WT-like gamma network dynamics and decreased Aβ plaque load. Conclusions We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs, inducing a network performance collapse. Moreover, our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.

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“…Examples of tauopathies are AD, some forms of Parkinsonism, and some frontotemporal dementias. complex 1 (mTORC1) pathway [13,14]. The resulting increase of nitroxidative stress and inflammatory mediators generates a persistent state of neuroinflammation similar to that observed in the brain during normal aging (Box 1).…”

Section: Trends In Pharmacological Sciencesmentioning

confidence: 99%

Toll-like receptor-mediated neuroinflammation: relevance for cognitive dysfunctions

Squillace

Salvemini

2022

Trends in Pharmacological Sciences

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TLR2- and TLR3-activated microglia induce different levels of neuronal network dysfunction in a context-dependent manner

Cited by 33 publications

References 94 publications

The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

Toll-like receptor-mediated neuroinflammation: relevance for cognitive dysfunctions

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