The effects of microglia‐ and astrocyte‐derived factors on neurogenesis in health and disease

Araki, Tasuku; Ikegaya, Yuji; Koyama, Ryuta

doi:10.1111/ejn.14969

Cited by 102 publications

(84 citation statements)

References 230 publications

(282 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacological intervention with compounds that show anti-inflammatory properties have demonstrated the neurodegenerative role of glial cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), following OP poisoning. However, it is important to mention that the secretion of other microglia- and astrocyte-derived factors that promote neurogenesis [ 37 ] may also contribute as a restorative effect following OP-induced seizure. Microglia have been implicated in the suppression of excess proliferation of neural stem cells and the inhibition of the formation of abnormal neural circuits by phagocytosis of adult-born granule cells in the epileptic dentate gyrus [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice

Marrero‐Rosado¹,

Stone²,

Furtado

et al. 2021

IJMS

View full text Add to dashboard Cite

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma. Carboxylesterase, an enzyme involved in the detoxification of some organophosphorus compounds, plays a scavenging role and decreases CWNA availability, thus exerting a protective effect. Furthermore, species-specific amino acid differences in acetylcholinesterase confound studies that use oximes or other compounds to restore its function after inhibition by CWNA. The creation of a human acetylcholinesterase knock-in/serum carboxylesterase knockout (C57BL/6-Ces1ctm1.1LocAChEtm1.1Loc/J; a.k.a KIKO) mouse may facilitate better modeling of CWNA toxicity in a small rodent species. The current studies characterize the effects of exposure to soman, a highly toxic CWNA, and evaluate the efficacy of anti-seizure drugs in this newly developed KIKO mouse model. Data demonstrate that a combination of midazolam and ketamine reduces seizure duration and severity, eliminates the development of spontaneous recurrent seizures, and protects certain brain regions from neuronal damage in a genetically modified model with human relevance to organophosphorus compound toxicity. This new animal model and the results of this study and future studies using it will enhance medical countermeasures development for both defense and homeland security purposes.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice

Marrero‐Rosado¹,

Stone²,

Furtado

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Among them, microglia are innate immune cells in the brain, while astrocytes are the key participants of central nervous system immune responses [ 47 , 48 ]. It has been reported that the activation of microglia was obviously increased in depression patients, and nerve damage induced by microglia is considered to be an important mechanism of depression [ 49 – 51 ]. In addition, some antidepressants, such as minocycline, can play a protective role by inhibiting the activation of microglia, oxidative stress, and inflammation [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Low‐Dose Copper Exposure Exacerbates Depression‐Like Behavior in ApoE4 Transgenic Mice

Zhang

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Depression is one of the most common neuropsychiatric disorders. Although the pathogenesis of depression is still unknown, environmental risk factors and genetics are implicated. Copper (Cu), a cofactor of multiple enzymes, is involved in regulating depression-related processes. Depressed patients carrying the apolipoprotein ε4 allele display more severe depressive symptoms, indicating that ApoE4 is closely associated with an increased risk of depression. The study explored the effect of low-dose Cu exposure and ApoE4 on depression-like behavior of mice and further investigates the possible mechanisms. The ApoE4 mice and wild-type (WT) mice were treated with 0.13 ppm CuCl2 for 4 months. After the treatment, ApoE4 mice displayed obvious depression-like behavior compared with the WT mice, and Cu exposure further exacerbated the depression-like behavior of ApoE4 mice. There was no significant difference in anxiety behavior and memory behavior. Proteomic analysis revealed that the differentially expressed proteins between Cu-exposed and nonexposed ApoE4 mice were mainly involved in the Ras signaling pathway, protein export, axon guidance, serotonergic synapse, GABAergic synapse, and dopaminergic synapse. Among these differentially expressed proteins, immune response and synaptic function are highly correlated. Representative protein expression changes are quantified by western blot, showing consistent results as determined by proteomic analysis. Hippocampal astrocytes and microglia were increased in Cu-exposed ApoE4 mice, suggesting that neuroglial cells played an important role in the pathogenesis of depression. Taken together, our study demonstrated that Cu exposure exacerbates depression-like behavior of ApoE4 mice and the mechanisms may involve the dysregulation of synaptic function and immune response and overactivation of neuroinflammation.

show abstract

“…Furthermore, mitochondria-derived from astrocytes rescue neurons whose mitochondria are damaged by stroke [ 10 ]. One mechanism by which they do this may be by secreting factors important for neurogenesis and neural function [ 37 ]. The treatment of culture medium of astrocytes from Fmr1 KO mice increases the percentage of large-size neurospheres but not the number of neurospheres, indicating that proteins secreted by astrocytes affect neural proliferation and differentiation [ 38 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome

Heo

Jang

et al. 2021

IJMS

View full text Add to dashboard Cite

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).

show abstract

The effects of microglia‐ and astrocyte‐derived factors on neurogenesis in health and disease

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 102 publications

References 230 publications

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice

Low‐Dose Copper Exposure Exacerbates Depression‐Like Behavior in ApoE4 Transgenic Mice

Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome

Contact Info

Product

Resources

About