Astrocyte-derived phosphatidic acid promotes dendritic branching

Zhu, Yan; Gao, Weizhen; Zhang, Yongbo; Feng, Jia; Zhang, Hai Long; Liu, Ying Zi; Sun, Xue Fang; Yin, Yuhua; Yin, Dong Min

doi:10.1038/srep21096

Cited by 32 publications

(25 citation statements)

References 41 publications

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“…Highlighting that phospholipids are not only the building support of these vesicles but those lipids themselves or their derivative-metabolites, could also carry a biological message. Supporting this notion, it was previously described that astrocyte-derived phosphatidic acid promotes dendritic branching 7 . Future investigation will focus in this hypothesis.…”

Section: Discussionmentioning

confidence: 72%

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Montaner

Santana

Schroeder

et al. 2018

Sci Rep

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Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.

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Section: Discussionmentioning

confidence: 72%

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Montaner

Santana

Schroeder

et al. 2018

Sci Rep

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“…If androgens stimulate dendritic growth in females, masculinised dendritic complexity might necessitate heightened astrocyte support and, in turn, increased astrocyte area . Conversely, androgenic actions on astrocytes might drive dendritic growth, as astrocytic factors can regulate dendritic branching and spine maturation …”

Section: Discussionmentioning

confidence: 99%

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Bollinger

Salinas

Fender

et al. 2019

J Neuroendocrinology

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Women are more susceptible to various stress‐linked psychopathologies, including depression. Dysfunction of the medial prefrontal cortex (mPFC) has been implicated in depression, and studies indicate sex differences in stress effects on mPFC structure and function. For example, chronic stress induces dendritic atrophy in the mPFC in male rats, yet dendritic growth in females. Recent findings suggest glial pathways toward depression. Glia are highly responsive to neuronal activity and function as critical regulators of synaptic plasticity. Preclinical models demonstrate stress‐induced microglial activation in mPFC in males, yet deactivation in females. By contrast, stress reduces astrocyte complexity in mPFC in male rats, whereas the effects in females are unknown. Glia possess receptors for most gonadal hormones and gonadal hormones are known to modulate neuronal activity. Thus, gonadal hormones represent a potential mechanism underlying sex differences in glia, as well as divergent stress effects. Therefore, we examined the role of gonadal hormones in sex‐specific stress effects on neuronal activity (ie FosB/ ΔFosB induction) and glia in the mPFC. The findings obtained indicate greater microglial activation in mPFC in females and a greater astrocyte area in males. Basal astrocyte morphology is modulated by androgens, whereas androgens or oestrogens dampen the microglial state in males. Astrocyte morphology is associated with neuronal activity in both sexes, regardless of hormonal condition. Chronic stress induced astrocytic atrophy in males, yet hypertrophy in females, with gonadal hormones partly regulating this difference. Stress effects on microglia are oestradiol‐dependent in females. Taken together, these data suggest sex‐specific, gonadal hormone‐dependent stress effects on astrocytes and microglia in the mPFC.

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“…Several studies have addressed the molecular mechanisms mediating the role of the astrocyte-derived secretome on dendritic morphology. To name some of these factors, it has been shown that astrocytes release phosphatidic acid to promote dendritic complexity in cultured hippocampal neurons as well as apolipoprotein E-complexed cholesterol and hevin to increase synaptogenesis in cultured retinal ganglion cells [4][5][6]. Very recently, it has also been shown that astrocyte-derived small extracellular vesicles (sEVs) act as regulators of cell functions and signaling in CNS cells, especially between astrocytes and neurons [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Luarte

Henzi

Fernández

et al. 2020

Cells

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In the last few decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP-tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) that are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e., GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation, but also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.

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Astrocyte-derived phosphatidic acid promotes dendritic branching

Cited by 32 publications

References 41 publications

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

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