Dexras1 is a homeostatic regulator of exercise-dependent proliferation and cell survival in the hippocampal neurogenic niche

Bouchard-Cannon, Pascale; Lowden, Christopher; Trinh, Dennison; Cheng, Hai-Ying Mary

doi:10.1038/s41598-018-23673-z

Cited by 14 publications

(11 citation statements)

References 85 publications

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“…Dexras1 is a small G protein activated by nitric oxide (NO), which is produced in activated microglia/macrophages or neurons [42]. The previous research on Dexras1 mainly focused on regulating circadian rhythms, tumor cell apoptosis, and other aspects [43,44].…”

Section: Discussionmentioning

confidence: 99%

Dexras1 Induces Dysdifferentiation of Oligodendrocytes by Inhibiting the cAMP-CREB Pathway in White Matter Injury After Subarachnoid Hemorrhage

Xin¹,

Zhang²,

Chen³

et al. 2021

Preprint

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BackgroundWhite matter damage (WMD), different from the widely studied neuronal death, is also involved in neurological dysfunction after subarachnoid hemorrhage (SAH) although the specific mechanism is not yet known. Dexras1 (RASD1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis; however, there is no information on whether Dexras1 participates in WMD after SAH. We hypothesized that Dexras1 participates in oligodendrocyte precursor cell (OPC) differentiation in WMD after SAH.MethodsIntracerebroventricular lentiviral administration was used to modulate Dexras1 levels to determine its functional influence on neurological injuries after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting were used to investigate the effects of Dexras1 on demyelination, glial cell activation and differentiation of OPCs after SAH. Primary rat brain neurons were treated with oxyhemoglobin to elucidate the association between Dexras1 and cAMP-CREB.ResultsDexras1 levels were significantly increased after SAH, accompanied by clear neurological deficits, glial cell activation, OPC differentiation disorders, and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH, which were accompanied by increased glial cell activation and levels of inflammatory factors. In contrast, Dexras1 knockdown ameliorated demyelination, oligodendrocyte differentiation disorders, and glial cell activation. cAMP acted as an upstream agonist of CREB, with decreased TNF-α and IL-1β levels after SAH. However, the cAMP-CREB pathway was inhibited after Dexras1 overexpression.ConclusionDexras1 induced oligodendrocyte dysdifferentiation after SAH and regulated glial cell activation through suppression of the cAMP-CREB pathway. This research highlights a novel direction for the improvement of neurological dysfunction after SAH.

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Section: Discussionmentioning

confidence: 99%

Dexras1 Induces Dysdifferentiation of Oligodendrocytes by Inhibiting the cAMP-CREB Pathway in White Matter Injury After Subarachnoid Hemorrhage

Xin¹,

Zhang²,

Chen³

et al. 2021

Preprint

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“…On the contrary, the positive role of exercise, especially in the case of previous brain impairment, is well assured (Lee et al, 2016 ; Mastrorilli et al, 2017 ). Finally, the impact on the hippocampus is more extensive and established (Lee et al, 2016 ; Mastrorilli et al, 2017 ; Snyder et al, 2017 ; Bouchard-Cannon et al, 2018 ; Firth et al, 2018 ; Masrour et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Reduction of Movement in Neurological Diseases: Effects on Neural Stem Cells Characteristics

et al. 2018

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Both astronauts and patients affected by chronic movement-limiting pathologies face impairment in muscle and/or brain performance. Increased patient survival expectations and the expected longer stays in space by astronauts may result in prolonged motor deprivation and consequent pathological effects. Severe movement limitation can influence not only the motor and metabolic systems but also the nervous system, altering neurogenesis and the interaction between motoneurons and muscle cells. Little information is yet available about the effect of prolonged muscle disuse on neural stem cells characteristics. Our in vitro study aims to fill this gap by focusing on the biological and molecular properties of neural stem cells (NSCs). Our analysis shows that NSCs derived from the SVZ of HU mice had shown a reduced proliferation capability and an altered cell cycle. Furthermore, NSCs obtained from HU animals present an incomplete differentiation/maturation. The overall results support the existence of a link between reduction of exercise and muscle disuse and metabolism in the brain and thus represent valuable new information that could clarify how circumstances such as the absence of load and the lack of movement that occurs in people with some neurological diseases, may affect the properties of NSCs and contribute to the negative manifestations of these conditions.

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“…Therefore, a global inhibition of caspase‐3 in the hippocampus would affect both types of cells. Recent experiments indicated aerobic exercise could activate quiescent RGL cells, making them enter the cell cycle more rapidly (Bouchard‐Cannon, Lowden, Trinh, & Cheng, ; Lugert et al, ). Moreover, caspase‐3 has been implicated in cell cycle regulation (Hashimoto, Kikkawa, & Kamada, ; Yan et al, ).…”

Section: Discussionmentioning

confidence: 99%

Astrocytes and radial glia‐like cells, but not neurons, display a nonapoptotic increase in caspase‐3 expression following exercise

2018

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BackgroundExercise induces plasticity in the hippocampus, which includes increases in neurogenesis, the proliferation of new neurons, and angiogenesis, the sprouting of new capillaries from preexisting blood vessels. Following exercise, astrocytes also undergo morphological changes that parallel the events occurring in the neurovascular system. Interestingly, there have also been reports of apoptosis in the hippocampus following aerobic exercise. This experiment aimed to identify which population of hippocampal cells undergoes apoptosis after an acute bout of exercise.MethodsCleaved caspase‐3, a terminal protein in the apoptotic cascade, was initially used to identify apoptotic cells in the hippocampus after rats completed an acute bout of exercise. Next, the proportion of immature neurons, adult neurons, astrocytes, or radial glia‐like cells expressing cleaved caspase‐3 was quantified. TUNEL staining was completed as a second measure of apoptosis.ResultsFollowing exercise, cleaved caspase‐3 expression was increased in the CA1 and DG regions of the hippocampus. Cleaved caspase‐3 was not highly expressed in neuronal populations, and expression was not increased in these cells postexercise. Instead, cleaved caspase‐3 was predominantly expressed in astrocytes. Following exercise, there was an increased number of cleaved caspase‐3 positive astrocytes in DG and CA1, and cleaved caspase‐3 positive radial glia‐like cells located in the subgranular zone. To determine whether cleaved caspase‐3 expression in these glial cells was associated with apoptosis, a TUNEL assay was completed. TUNEL staining was negligible in all groups and did not mirror the pattern of caspase‐3 labeling.ConclusionsCleaved caspase‐3 expression was detected largely in non‐neuronal cell populations, and the pattern of cleaved caspase‐3 expression did not match that of TUNEL. This suggests that after exercise, cleaved caspase‐3 expression may serve a nonapoptotic role in these hippocampal astrocytes and radial glia‐like cells. It will be important to identify the function of exercise‐induced cleaved caspase‐3 expression in the future experiments.

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Dexras1 is a homeostatic regulator of exercise-dependent proliferation and cell survival in the hippocampal neurogenic niche

Cited by 14 publications

References 85 publications

Dexras1 Induces Dysdifferentiation of Oligodendrocytes by Inhibiting the cAMP-CREB Pathway in White Matter Injury After Subarachnoid Hemorrhage

Dexras1 Induces Dysdifferentiation of Oligodendrocytes by Inhibiting the cAMP-CREB Pathway in White Matter Injury After Subarachnoid Hemorrhage

Reduction of Movement in Neurological Diseases: Effects on Neural Stem Cells Characteristics

Astrocytes and radial glia‐like cells, but not neurons, display a nonapoptotic increase in caspase‐3 expression following exercise

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