Regulation of Synaptic Development by Astrocyte Signaling Factors and Their Emerging Roles in Substance Abuse

Walker, Christopher D.; Risher, W. Christopher; Risher, Mary-Louise

doi:10.3390/cells9020297

Cited by 26 publications

(12 citation statements)

References 80 publications

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“…Furthermore, these drugs disrupt complex interactions in the brain linked to astrocytes that engage in crosstalk with neurons. These subsequently lead to a variety of CNS dysfunctions, including effects on neurogenesis and synaptic diversity [8]. Astrocytes play an essential role in energy metabolism, neurotransmission, and the inflammatory process [9].…”

Section: Introductionmentioning

confidence: 99%

“…Astrocytes play an essential role in energy metabolism, neurotransmission, and the inflammatory process [9]. Epigenetic modifications in the transcriptional machinery of astrocytes may drive astrocyte reactivity, thereby contributing to neuronal injury due to psychostimulant and opioid abuse [8]. Therefore, astrocytes are being recognized as promising targets for neuroprotective drugs [10].…”

Section: Introductionmentioning

confidence: 99%

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Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

2021

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Illicit drugs are known to affect central nervous system (CNS). Majorly psychostimulants such as cocaine, methamphetamine (METH) and opioids such as morphine are known to induce epigenetic changes of histone modifications and chromatin remodeling which are mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Aberrant changes in histone acetylation-deacetylation process further exacerbate dysregulation of gene expression and protein modification which has been linked with neuronal impairments including memory formation and synaptic plasticity. In CNS, astrocytes play a pivotal role in cellular homeostasis. However, the impact of psychostimulants and opioid mediated epigenetic changes of HAT/HADCs in astrocytes has not yet been fully elucidated. Therefore, we have investigated the effects of the psychostimulants and opioid on the acetylation-regulating enzymes- HAT and HDACs role in astrocytes. In this study, Class I and II HDACs and HATs gene expression, protein changes and global level changes of acetylation of H3 histones at specific lysines were analyzed. In addition, we have explored the neuroprotective “nootropic” drug piracetam were exposed with or without psychostimulants and opioid in the human primary astrocytes. Results revealed that psychostimulants and opioid upregulated HDAC1, HDAC4 and p300 expression, while HDAC5 and GCN5 expression were downregulated. These effects were reversed by piracetam coexposure. Psychostimulants and opioid exposure upregulated global acetylation levels of all H3Ks, except H3K14. These results suggest that psychostimulants and opioids differentially influence HATs and HDACs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

2021

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“…The most frequent type of glial cells are oligodendrocytes (45–75%), followed by astrocytes (19–40%) and microglia (around 10%) [ 63 ]. In recent years, a significant amount of data was collected indicating that glial cells are not passive elements of the white matter but are actively involved in synaptic development and plasticity and in the regulation of neuronal activity through tripartite synapses [ 64 , 65 , 66 , 67 ]. Glial cells could significantly impact the information flow in the cortical circuitry by influencing WMIN (see WMIN function below).…”

Section: Total Neuronal Number Density and Spatial Distribution mentioning

confidence: 99%

White Matter Interstitial Neurons in the Adult Human Brain: 3% of Cortical Neurons in Quest for Recognition

Sedmak

Judaš

2021

Cells

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White matter interstitial neurons (WMIN) are a subset of cortical neurons located in the subcortical white matter. Although they were fist described over 150 years ago, they are still largely unexplored and often considered a small, functionally insignificant neuronal population. WMIN are adult remnants of neurons located in the transient fetal subplate zone (SP). Following development, some of the SP neurons undergo apoptosis, and the remaining neurons are incorporated in the adult white matter as WMIN. In the adult human brain, WMIN are quite a large population of neurons comprising at least 3% of all cortical neurons (between 600 and 1100 million neurons). They include many of the morphological neuronal types that can be found in the overlying cerebral cortex. Furthermore, the phenotypic and molecular diversity of WMIN is similar to that of the overlying cortical neurons, expressing many glutamatergic and GABAergic biomarkers. WMIN are often considered a functionally unimportant subset of neurons. However, upon closer inspection of the scientific literature, it has been shown that WMIN are integrated in the cortical circuitry and that they exhibit diverse electrophysiological properties, send and receive axons from the cortex, and have active synaptic contacts. Based on these data, we are able to enumerate some of the potential WMIN roles, such as the control of the cerebral blood flow, sleep regulation, and the control of information flow through the cerebral cortex. Also, there is a number of studies indicating the involvement of WMIN in the pathophysiology of many brain disorders such as epilepsy, schizophrenia, Alzheimer’s disease, etc. All of these data indicate that WMIN are a large population with an important function in the adult brain. Further investigation of WMIN could provide us with novel data crucial for an improved elucidation of the pathophysiology of many brain disorders. In this review, we provide an overview of the current WMIN literature, with an emphasis on studies conducted on the human brain.

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“…Neuro inflammation-induced A1 astrocytes to secrete neurotoxins that in turn induced rapid death in neurons and oligodendrocytes. The C3, CFB, and MX1S are the genes expressed in type A1 and considered as markers in this type of astrocyte [ [14] , [16] ]. The A1 astrocytes lose many of their normal functions, such as contributing to neuronal viability and growth, inducing fewer and weaker synapses than common astrocytes, and progressive killing of adult neurons.…”

Section: Introductionmentioning

confidence: 99%

More attention on glial cells to have better recovery after spinal cord injury

Hassanzadeh

Jalessi

Jameie

et al. 2021

Biochemistry and Biophysics Reports

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Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury.

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Regulation of Synaptic Development by Astrocyte Signaling Factors and Their Emerging Roles in Substance Abuse

Cited by 26 publications

References 80 publications

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

White Matter Interstitial Neurons in the Adult Human Brain: 3% of Cortical Neurons in Quest for Recognition

More attention on glial cells to have better recovery after spinal cord injury

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