Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP

Yang, Junhua; Yang, Hong-Chang; Liu, Yali; Li, Xia; Qin, Liqiang; Lou, Huifang; Duan, Shumin; Wang, Hao

doi:10.7554/elife.15043

Cited by 77 publications

(53 citation statements)

References 49 publications

(63 reference statements)

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“…The ability to release ACh is a decisive factor in the stabilization or loss of motor nerve terminals that are in competition to make synapses during development [15,16,18,[25][26][27] . Postsynaptic-derived trophic substances [20] and glial cells [28,29] also play a decisive role.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction

Nadal

García²,

Hurtado³

et al. 2016

Dev Neurosci

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The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M₁, M₂, and M₄ subtypes) and adenosine receptors (A₁ and A_2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo. In a previous study we analyzed the role of each of the individual receptors. Here we investigate the additive or occlusive effects of their inhibitors and thus the existence of synergistic activity between the receptors. The main results show that the A_2A, M₁, M₄, and A₁ receptors (in this order of ability) delayed axonal elimination at P7. M₄ produces some occlusion of the M₁ pathway and some addition to the A₁ pathway, which suggests that they cooperate. M₂ receptors may modulate (by allowing a permissive action) the other receptors, mainly M₄ and A₁. The continued action of these receptors (now including M₂ but not M₄) finally promotes axonal loss at P9. All 4 receptors (M₂, M₁, A₁, and A_2A, in this order of ability) are necessary. The M₄ receptor (which in itself does not affect axon loss) seems to modulate the other receptors. We found a synergistic action between the M₁, A₁, and A_2A receptors, which show an additive effect, whereas the potent M₂ effect is largely independent of the other receptors (though can be modulated by M₄). At P9, there is a full mutual dependence between the A₁ and A_2A receptors in regulating axon loss. In summary, postnatal axonal elimination is a regulated multireceptor mechanism that involves the cooperation of several muscarinic and adenosine receptor subtypes.

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Section: Discussionmentioning

confidence: 99%

Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction

Nadal

García²,

Hurtado³

et al. 2016

Dev Neurosci

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“…The most studies have focused on the roles of astrocytes or microglia on synapse formation/maturation or elimination, respectively. However, several studies have suggested the opposite roles: that is, astrocyte‐mediated synapse elimination (Chung et al, ; Chung et al, ; Yang et al, ) or microglia‐induced synapse formation (Miyamoto et al, ; Parkhurst et al, ). Because synapse elimination is also important for brain pathology in addition to synapse formation, further studies are required to resolve this issue.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Astrocyte‐mediated synapse remodeling in the pathological brain

Kim

Nabekura

Koizumi

2017

Glia

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Astrocytes, a major type of glia, reciprocally influence synaptic transmission and connectivity, forming the "tripartite synapses". Astrocytic metabotropic glutamate receptor (mGluR)-mediated Ca waves and release of gliotransmitters or synaptogenic molecules mediate this neuron-glia interaction in the developing brain, but this signaling has been challenged for adult brain. However, cumulative evidence has suggested that mature astrocytes exhibit re-awakening of such immature phenotype in the pathological adult brain. This phenotypic change in astrocytes in response to injury may induce neural circuit and synapse plasticity. In this review article, we summarize astrocyte-mediated synapse remodeling during physiological development, discuss re-emergence of immature astrocytic signaling in adult pathological brain, and finally highlight its contribution to significant modification of synaptic connections correlating with functional progress of brain pathology.

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“…Neuroimmune cells, such as microglia (Schafer et al, ) and astrocytes (Chung et al, ), are important players in pruning given their ability to phagocytose unwanted synapses. Several molecular mechanisms have been proposed to mediate pruning, such as the classical complement pathway (Stevens et al, ) or inositol 1,4,5‐trisphosphate (Yang et al, ). However, those studies have focused on early visual retinogeniculate circuitry development stages, and it remains unclear whether similar mechanisms can play a role in adolescence.…”

Section: Introductionmentioning

confidence: 99%

Role of the innate immune system in the neuropathological consequences induced by adolescent binge drinking

Pascual

Montesinos

2017

J of Neuroscience Research

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Adolescence is a critical stage of brain maturation in which important plastic and dynamic processes take place in different brain regions, leading to development of the adult brain. Ethanol drinking in adolescence disrupts brain plasticity and causes structural and functional changes in immature brain areas (prefrontal cortex, limbic system) that result in cognitive and behavioral deficits. These changes, along with secretion of sexual and stress-related hormones in adolescence, may impact self-control, decision making, and risk-taking behaviors that contribute to anxiety and initiation of alcohol consumption. New data support the participation of the neuroimmune system in the effects of ethanol on the developing and adult brain. This article reviews the potential pathological bases that underlie the effects of alcohol on the adolescent brain, such as the contribution of genetic background, the perturbation of epigenetic programming, and the influence of the neuroimmune response. Special emphasis is given to the actions of ethanol in the innate immune receptor toll-like receptor 4 (TLR4), since recent studies have demonstrated that by activating the inflammatory TLR4/NFκB signaling response in glial cells, binge drinking of ethanol triggers the release of cytokines/chemokines and free radicals, which exacerbate the immune response that causes neuroinflammation/neural damage as well as short- and long-term neurophysiological, cognitive, and behavioral dysfunction. Finally, potential treatments that target the neuroimmune response to treat the neuropathological and behavioral consequences of adolescent alcohol abuse are discussed.

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Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP

Cited by 77 publications

References 49 publications

Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction

Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction

Astrocyte‐mediated synapse remodeling in the pathological brain

Role of the innate immune system in the neuropathological consequences induced by adolescent binge drinking

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