Phospholipase C β3 is Required for Climbing Fiber Synapse Elimination in Aldolase C-positive Compartments of the Developing Mouse Cerebellum

Rai, Yurie; Watanabe, Takaki; Matsuyama, Kiminori; Sakimura, Kenji; Uesaka, Naofumi; Kano, Masanobu

doi:10.1016/j.neuroscience.2020.04.035

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Over the years, ALDOC has been found to be particularly abundant in brain tissue. It is present in normal brain tissue and is responsible for repairing damaged tissue [47][48][49]. In this study, both ALDOC and ALDOA were upregulated during hypoxia, which is consistent with [47]; it can be hypothesized that hypoxia induces the Warburg effect to acquire glycolysis and improve the survival of PASMCs by upregulating the expression of ALDOC and other related genes (p < 0.05).…”

Section: Discussionsupporting

confidence: 85%

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

Zhang,

Zhou,

Liang

et al. 2023

Animals

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The aim of this study was to investigate the molecular mechanisms by which hypoxia affects the biological behavior of yak PASMCs, the changes in the histological structure of yak and cattle lungs, and the relationships and regulatory roles that exist regarding the differences in the distribution and expression of PDK1 and its hypoxia−associated factors screened for their role in the adaptation of yak lungs to the plateau hypoxic environment. The results showed that, at the level of transcriptome sequencing, the molecular regulatory mechanisms of the HIF−1 signaling pathway, glucose metabolism pathway, and related factors (HK2/PGK1/ENO1/ENO3/ALDOC/ALDOA) may be closely related to the adaptation of yaks to the hypoxic environment of the plateau; at the tissue level, the presence of filled alveoli and semi−filled alveoli, thicker alveolar septa and basement membranes, a large number of erythrocytes, capillary distribution, and collagen fibers accounted for all levels of fine bronchioles in the lungs of yaks as compared to cattle. A higher percentage of goblet cells was found in the fine bronchioles of yaks, and PDK1, HIF−1α, and VEGF were predominantly distributed and expressed in the monolayers of ciliated columnar epithelium in the branches of the terminal fine bronchioles of yak and cattle lungs, with a small amount of it distributed in the alveolar septa; at the molecular level, the differences in PDK1 mRNA relative expression in the lungs of adult yaks and cattle were not significant (p > 0.05), the differences in HIF−1α and VEGF mRNA relative expression were significant (p < 0.05), and the expression of PDK1 and HIF−1α proteins in adult yaks was stronger than that in adult cattle. PDK1 and HIF−1α proteins were more strongly expressed in adult yaks than in adult cattle, and the difference was highly significant (p < 0.01); the relative expression of VEGF proteins was not significantly different between adult yaks and cattle (p > 0.05). The possible regulatory relationship between the above results and the adaptation of yak lungs to the plateau hypoxic environment paves the way for the regulatory mechanisms of PDK1, HIF−1α, and VEGF, and provides basic information for studying the mechanism of hypoxic adaptation of yaks in the plateau. At the same time, it provides a reference for human hypoxia adaptation and a target for the prevention and treatment of plateau diseases in humans and plateau animals.

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Section: Discussionsupporting

confidence: 85%

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

Zhang,

Zhou,

Liang

et al. 2023

Animals

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“…The heterosynaptic interaction in PCs derived from direct activation of mGlu1 at PF-PC synapses and indirect enhancement of GABAergic inhibition onto PCs involving NMDA receptors in MLIs. While mGlu1 has been shown to trigger signaling cascades in PCs involving Gαq 37 , PLCβ3 and PLCβ4 36 , 38 , PKCγ 35 , Semaphorin 7 A 77 , and BDNF 78 , it is not well understood how GABAergic inhibition regulates CF synapse elimination. Whether these two pathways converge or act independently in PCs to eliminate redundant CF synapses to establish mature synaptic wiring in the cerebellum remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study suggests that mGlu1 can be activated at CF synapses particularly when glutamate uptake is inhibited 29 . However, mGlu1 is thought to be functional predominantly at PF synapses 30 – 34 and trigger signaling cascades involving Gαq, PLCβ3/4, and PKCγ in PCs to fuel CF synapse elimination 35 – 38 . This argument that mGlu1 is activated at PF-PC synapses is based on the results that NMDA-type glutamate receptors (NMDARs) within the cerebellum are required for CF synapse elimination 39 during the third postnatal week 40 although functional NMDARs are lacking in PCs during this developmental stage 40 – 42 .…”

Section: Introductionmentioning

confidence: 99%

Direct and indirect pathways for heterosynaptic interaction underlying developmental synapse elimination in the mouse cerebellum

Nakayama,

Miyazaki,

Abe

et al. 2024

Commun Biol

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Developmental synapse elimination is crucial for shaping mature neural circuits. In the neonatal mouse cerebellum, Purkinje cells (PCs) receive excitatory synaptic inputs from multiple climbing fibers (CFs) and synapses from all but one CF are eliminated by around postnatal day 20. Heterosynaptic interaction between CFs and parallel fibers (PFs), the axons of cerebellar granule cells (GCs) forming excitatory synapses onto PCs and molecular layer interneurons (MLIs), is crucial for CF synapse elimination. However, mechanisms for this heterosynaptic interaction are largely unknown. Here we show that deletion of AMPA-type glutamate receptor functions in GCs impairs CF synapse elimination mediated by metabotropic glutamate receptor 1 (mGlu1) signaling in PCs. Furthermore, CF synapse elimination is impaired by deleting NMDA-type glutamate receptors from MLIs. We propose that PF activity is crucial for CF synapse elimination by directly activating mGlu1 in PCs and indirectly enhancing the inhibition of PCs through activating NMDA receptors in MLIs.

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Cerebellar Molecular Signatures in Non‐Human Primates

Yamamoto,

Yoshida,

Ose

et al. 2024

J of Comparative Neurology

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Cerebellar molecular signatures in primates remain largely unexplored. Here, we investigated the immunoreactivity of neuroplasticity‐related molecular markers, including aldolase C (Aldoc), phospholipase C beta 3 (PLCB3), and phospholipase C beta 4 (PLCB4) in the cerebellar cortex and associated nuclei of rhesus macaque monkeys (Macaca mulatta). Our main findings are as follows: First, the cerebellar vermis in macaques exhibited striped compartmentalization for all markers, with the striped expression boundary of PLCB3 being less distinct than those of Aldoc and PLCB4. Second, the striped pattern was less pronounced in the cerebellar hemisphere compared to the vermis, with signals in the hemisphere being predominantly intense throughout. Third, distinct zonal patterns and elevated signals for Aldoc and PLCB3 were observed in the cerebellar deep nuclei. Specifically, the fastigial nucleus displayed intense Aldoc signals in both caudal and rostral regions, while the dentate nucleus displayed strong Aldoc signals in both ventral and dorsal regions. Compared to previous rodent studies, the macaque cerebellum demonstrated a higher proportion of intense signal areas and distinct compartmentalization patterns in both cortical and deep nuclei. These findings offer crucial insights into the unique molecular organization of the primate cerebellum, enhancing our understanding of the advanced neuroplasticity, cognitive, and motor capabilities in primates.

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Phospholipase C β3 is Required for Climbing Fiber Synapse Elimination in Aldolase C-positive Compartments of the Developing Mouse Cerebellum

Cited by 7 publications

References 27 publications

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

Direct and indirect pathways for heterosynaptic interaction underlying developmental synapse elimination in the mouse cerebellum

Cerebellar Molecular Signatures in Non‐Human Primates

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