Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice

Preez, Andrea Du; Onorato, Diletta; Eiben, Inez; Musaelyan, Ksenia; Egeland, Martin; Zunszain, Patricia A.; Fernandes, Cathy; Thuret, Sandrine; Pariante, Carmine M.

doi:10.1016/j.bbi.2020.07.015

Cited by 173 publications

(86 citation statements)

References 152 publications

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“…As is well known, lead is a heavy metal pollutant in industrial production and daily life environment [17]. Nerve damage caused by lead exposure has always been a public health concern, but little is known about its precise molecular mechanism [18][19][20]. Exosomal microRNAs play a certain role in the occurrence and development of neurodegenerative diseases and the research of their biomarkers [21,22].…”

Section: Introductionmentioning

confidence: 99%

Statistical Analysis for Identifying Differentially MicroRNA in Serum Exosomes of Lead Workers

Shi

Wang

et al. 2020

Journal of Healthcare Engineering

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Exosomes can transmit central nervous system (CNS) information to the peripheral circulatory system through the brain barrier, and exosomes in the blood can also enter the central nervous system likewise. The components of exosomal contents play a pivotal role in cell signal communication, and thus, the transmission of exosomal content components is considered as a newly discovered method of long-distance communication between cells. The current is aimed to explore the changes of the exosomal microRNA group in the serum of lead-exposed workers, which might be involved in the lead-induced neuroinflammation, especially the activation of microglia and the release of inflammatory factors. We proposed a method combining statistical analysis and experiment according to the different expression of exosomal microRNA. Firstly, we divided workers into two groups, lead-exposed group and control group, and then questionnaires were used to obtain their basic information, and medical testing methods were used to obtain their serum exosomes. Secondly, principal component analysis was used to construct a comprehensive index of neurobehavioral function. Furthermore, volcano map and heatmap were used to display the differential gene distribution and correlation analysis of expression levels, respectively. Finally, two software applications, TargetScan and miRanda, were used to predict the target genes of the significantly different microRNAs, respectively, and the target genes predicted by the two software applications are screened according to the scoring standards of each software. Our results showed that 73 microRNAs were changed in the serum exosomes of lead-exposed worker, among which 48 microRNAs are upregulated and 25 microRNAs are downregulated. Moreover, the miR-124 and miR-506 were identified, and they might be involved in the process of lead-induced neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

Statistical Analysis for Identifying Differentially MicroRNA in Serum Exosomes of Lead Workers

Shi

Wang

et al. 2020

Journal of Healthcare Engineering

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“…It is well known that interfering with adult hippocampal neurogenesis can results in depressive-like behavioral changes (Anacker and Hen, 2017). Conversely, many animal models of depression show impaired hippocampal neurogenesis (Du Preez et al, 2021). It is thus possible that the behavioral phenotype of GLAST-CreERT2-Dagla KO mice was at least partially due the impaired hippocampal neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Autocrine regulation of adult neurogenesis by the endocannabinoid 2-arachidonoylglycerol (2-AG)

Schuele

Schürmann

Bilkei-Gorzó

et al. 2021

Preprint

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The endocannabinoid system (ECS) modulates adult hippocampal neurogenesis by promoting the proliferation and survival of progenitor cells. Specifically, deleting cannabinoid CB1 receptors on neuronal stem cells (NSCs) or the constitutive deletion of the endocannabinoid 2-arachidonoylglycerol (2-AG) producing enzyme diacylglycerol lipase alpha (DAGLa) disrupts adult hippocampal neurogenesis. However, it is not known which cells are the producers of 2-AG relevant to neurogenesis. In this paper, we investigated the cellular source of endocannabinoids in the subgranular zone (SGZ) of the hippocampus, an important neurogenic niche. For this purpose, we used two complementary Cre-deleter mouse strains to delete DAGLa either in neurons or astroglia and neuronal progenitor cells. Surprisingly, neurogenesis was not altered in mice with a specific deletion of Dagla in neurons (Syn-Dagla KO), although these cells are the main source for the endocannabinoids in the brain. In contrast, mice with a specific inducible deletion of Dagla in neuronal progenitor cells and astrocytes (GLAST-CreERT2-Dagla KO) showed a strongly impaired neurogenesis with significantly reduced proliferation and survival of newborn cells. These results identify Dagla in neuronal progenitor cells in the SGZ of dentate gyrus or in astrocytes, as the cellular source for 2-AG in adult hippocampal neurogenesis. In summary, 2-AG produced by progenitor cells or astrocytes in the SGZ regulates adult hippocampal neurogenesis. The implications of these findings and the depressive-like phenotype in Dagla-deficient genetic mouse models are discussed.

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“…Chronic stress alters glial function and, just like CBD, pharmacological or genetic targeting these stress-induced changes modify its behavioral and neuroplastic consequences. Chronic stress increases astrocyte number and microglial activation in the dentate gyrus of the hippocampus ( Machado-Santos et al, 2019 ; Du Preez et al, 2020 ). Yu et al (2019) showed that chronic stress decreases the expression of the astroglial glutamate transporter-1 (GLT-1) in the hippocampus after ischemic stroke, which was accompanied by impaired synaptic plasticity and depressive-like behavior.…”

Section: Cbd Effects That Not Include Glial Cells In Its Mechanism Ofmentioning

confidence: 99%

Glial Cells and Their Contribution to the Mechanisms of Action of Cannabidiol in Neuropsychiatric Disorders

et al. 2021

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Cannabidiol (CBD) is a phytocannabinoid with a broad-range of therapeutic potential in several conditions, including neurological (epilepsy, neurodegenerative diseases, traumatic and ischemic brain injuries) and psychiatric disorders (schizophrenia, addiction, major depressive disorder, and anxiety). The pharmacological mechanisms responsible for these effects are still unclear, and more than 60 potential molecular targets have been described. Regarding neuropsychiatric disorders, most studies investigating these mechanisms have focused on neuronal cells. However, glial cells (astrocytes, oligodendrocytes, microglia) also play a crucial role in keeping the homeostasis of the central nervous system. Changes in glial functions have been associated with neuropathological conditions, including those for which CBD is proposed to be useful. Mostly in vitro studies have indicated that CBD modulate the activation of proinflammatory pathways, energy metabolism, calcium homeostasis, and the proliferative rate of glial cells. Likewise, some of the molecular targets proposed for CBD actions are f expressed in glial cells, including pharmacological receptors such as CB1, CB2, PPAR-γ, and 5-HT1A. In the present review, we discuss the currently available evidence suggesting that part of the CBD effects are mediated by interference with glial cell function. We also propose additional studies that need to be performed to unveil the contribution of glial cells to CBD effects in neuropsychiatric disorders.

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Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice

Cited by 173 publications

References 152 publications

Statistical Analysis for Identifying Differentially MicroRNA in Serum Exosomes of Lead Workers

Statistical Analysis for Identifying Differentially MicroRNA in Serum Exosomes of Lead Workers

Autocrine regulation of adult neurogenesis by the endocannabinoid 2-arachidonoylglycerol (2-AG)

Glial Cells and Their Contribution to the Mechanisms of Action of Cannabidiol in Neuropsychiatric Disorders

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