Brain Sciences

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Open AccessFeature PaperReview

Impact of Increased Astrocyte Expression of IL-6, CCL2 or CXCL10 in Transgenic Mice on Hippocampal Synaptic Function

by Donna L. Gruol

Brain Sci. 2016, 6(2), 19; https://doi.org/10.3390/brainsci6020019 - 17 Jun 2016

Cited by 24 | Viewed by 6359

An important aspect of CNS disease and injury is the elevated expression of neuroimmune factors. These factors are thought to contribute to processes ranging from recovery and repair to pathology. The complexity of the CNS and the multitude of neuroimmune factors that are [...] Read more.

An important aspect of CNS disease and injury is the elevated expression of neuroimmune factors. These factors are thought to contribute to processes ranging from recovery and repair to pathology. The complexity of the CNS and the multitude of neuroimmune factors that are expressed in the CNS during disease and injury is a challenge to an understanding of the consequences of the elevated expression relative to CNS function. One approach to address this issue is the use of transgenic mice that express elevated levels of a specific neuroimmune factor in the CNS by a cell type that normally produces it. This approach can provide basic information about the actions of specific neuroimmune factors and can contribute to an understanding of more complex conditions when multiple neuroimmune factors are expressed. This review summarizes studies using transgenic mice that express elevated levels of IL-6, CCL2 or CXCL10 through increased astrocyte expression. The studies focus on the effects of these neuroimmune factors on synaptic function at the Schaffer collateral to CA1 pyramidal neuron synapse of the hippocampus, a brain region that plays a key role in cognitive function. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

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Open AccessArticle

Neuroimmunology of the Interleukins 13 and 4

by Simone Mori, Pamela Maher and Bruno Conti

Brain Sci. 2016, 6(2), 18; https://doi.org/10.3390/brainsci6020018 - 13 Jun 2016

Cited by 78 | Viewed by 8507

Abstract

The cytokines interleukin 13 and 4 share a common heterodimeric receptor and are important modulators of peripheral allergic reactions. Produced primarily by T-helper type 2 lymphocytes, they are typically considered as anti-inflammatory cytokines because they can downregulate the synthesis of T-helper type 1 [...] Read more.

The cytokines interleukin 13 and 4 share a common heterodimeric receptor and are important modulators of peripheral allergic reactions. Produced primarily by T-helper type 2 lymphocytes, they are typically considered as anti-inflammatory cytokines because they can downregulate the synthesis of T-helper type 1 pro-inflammatory cytokines. Their presence and role in the brain is only beginning to be investigated and the data collected so far shows that these molecules can be produced by microglial cells and possibly by neurons. Attention has so far been given to the possible role of these molecules in neurodegeneration. Both neuroprotective or neurotoxic effects have been proposed based on evidence that interleukin 13 and 4 can reduce inflammation by promoting the M2 microglia phenotype and contributing to the death of microglia M1 phenotype, or by potentiating the effects of oxidative stress on neurons during neuro-inflammation. Remarkably, the heterodimeric subunit IL-13Rα1 of their common receptor was recently demonstrated in dopaminergic neurons of the ventral tegmental area and the substantia nigra pars compacta, suggesting the possibility that both cytokines may affect the activity of these neurons regulating reward, mood, and motor coordination. In mice and man, the gene encoding for IL-13Rα1 is expressed on the X chromosome within the PARK12 region of susceptibility to Parkinson’s disease (PD). This, together with finding that IL-13Rα1 contributes to loss of dopaminergic neurons during inflammation, indicates the possibility that these cytokines may contribute to the etiology or the progression of PD. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

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Open AccessDiscussion

Parkinson’s Disease: Assay of Phosphorylated α-Synuclein in Skin Biopsy for Early Diagnosis and Association with Melanoma

by Andrei Surguchov

Brain Sci. 2016, 6(2), 17; https://doi.org/10.3390/brainsci6020017 - 26 May 2016

Cited by 8 | Viewed by 7611

Abstract

Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, in which a small naturally unfolded protein α-synuclein plays an essential role. α-Synuclein belongs to a synuclein family comprising three members: α, β, and γ-synucleins associated with neurodegenerative and neoplastic diseases [...] Read more.

Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, in which a small naturally unfolded protein α-synuclein plays an essential role. α-Synuclein belongs to a synuclein family comprising three members: α, β, and γ-synucleins associated with neurodegenerative and neoplastic diseases and involved in development. Several studies revealed that α-synuclein is present not only in the brain, but also in the skin and other peripheral tissues. This finding open a new approach to PD diagnosis based on the assay of α-synuclein from a biological sample of a living patient. Furthermore, PD is associated with an increased risk of skin melanoma. An important posttranslational modification of α-synuclein is phosphorylation at serine-129, which may convert the protein into pathological species both in PD and melanoma. Thus, analysis of phosphorylated α-synuclein might be an important diagnostic test for both diseases providing additional information about the mechanism of pathology. Full article

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Open AccessArticle

Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration

by Simon Alex Marshall, Chelsea Rhea Geil and Kimberly Nixon

Brain Sci. 2016, 6(2), 16; https://doi.org/10.3390/brainsci6020016 - 26 May 2016

Cited by 79 | Viewed by 7810

Abstract

Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced [...] Read more.

Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

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Open AccessArticle

Astrocytic IL-6 Influences the Clinical Symptoms of EAE in Mice

by Maria Erta, Mercedes Giralt, Silvia Jiménez, Amalia Molinero, Gemma Comes and Juan Hidalgo

Brain Sci. 2016, 6(2), 15; https://doi.org/10.3390/brainsci6020015 - 17 May 2016

Cited by 22 | Viewed by 6030

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells [...] Read more.

Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

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Open AccessReview

Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI

by Elena Bilevicius, Tiffany A. Kolesar and Jennifer Kornelsen

Brain Sci. 2016, 6(2), 14; https://doi.org/10.3390/brainsci6020014 - 19 Apr 2016

Cited by 16 | Viewed by 6128

Abstract

Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two [...] Read more.

Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. Full article

(This article belongs to the Special Issue Functional Neuroimaging of Pain)

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Open AccessArticle

Wisteria Floribunda Agglutinin-Labeled Perineuronal Nets in the Mouse Inferior Colliculus, Thalamic Reticular Nucleus and Auditory Cortex

by Sarah M. Fader, Kazuo Imaizumi, Yuchio Yanagawa and Charles C. Lee

Brain Sci. 2016, 6(2), 13; https://doi.org/10.3390/brainsci6020013 - 13 Apr 2016

Cited by 17 | Viewed by 6657

Abstract

Perineuronal nets (PNNs) are specialized extracellular matrix molecules that are associated with the closing of the critical period, among other functions. In the adult brain, PNNs surround specific types of neurons, however the expression of PNNs in the auditory system of the mouse, [...] Read more.

Perineuronal nets (PNNs) are specialized extracellular matrix molecules that are associated with the closing of the critical period, among other functions. In the adult brain, PNNs surround specific types of neurons, however the expression of PNNs in the auditory system of the mouse, particularly at the level of the midbrain and forebrain, has not been fully described. In addition, the association of PNNs with excitatory and inhibitory cell types in these structures remains unknown. Therefore, we sought to investigate the expression of PNNs in the inferior colliculus (IC), thalamic reticular nucleus (TRN) and primary auditory cortex (A1) of the mouse brain by labeling with wisteria floribunda agglutinin (WFA). To aid in the identification of inhibitory neurons in these structures, we employed the vesicular GABA transporter (VGAT)-Venus transgenic mouse strain, which robustly expresses an enhanced yellow-fluorescent protein (Venus) natively in nearly all gamma-amino butyric acid (GABA)-ergic inhibitory neurons, thus enabling a rapid and unambiguous assessment of inhibitory neurons throughout the nervous system. Our results demonstrate that PNNs are expressed throughout the auditory midbrain and forebrain, but vary in their local distribution. PNNs are most dense in the TRN and least dense in A1. Furthermore, PNNs are preferentially associated with inhibitory neurons in A1 and the TRN, but not in the IC of the mouse. These data suggest regionally specific roles for PNNs in auditory information processing. Full article

(This article belongs to the Special Issue Auditory System)

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Open AccessReview

Epigenetic Mechanisms in Developmental Alcohol-Induced Neurobehavioral Deficits

by Balapal S. Basavarajappa and Shivakumar Subbanna

Brain Sci. 2016, 6(2), 12; https://doi.org/10.3390/brainsci6020012 - 08 Apr 2016

Cited by 49 | Viewed by 9247

Abstract

Alcohol consumption during pregnancy and its damaging consequences on the developing infant brain are significant public health, social, and economic issues. The major distinctive features of prenatal alcohol exposure in humans are cognitive and behavioral dysfunction due to damage to the central nervous [...] Read more.

Alcohol consumption during pregnancy and its damaging consequences on the developing infant brain are significant public health, social, and economic issues. The major distinctive features of prenatal alcohol exposure in humans are cognitive and behavioral dysfunction due to damage to the central nervous system (CNS), which results in a continuum of disarray that is collectively called fetal alcohol spectrum disorder (FASD). Many rodent models have been developed to understand the mechanisms of and to reproduce the human FASD phenotypes. These animal FASD studies have provided several molecular pathways that are likely responsible for the neurobehavioral abnormalities that are associated with prenatal alcohol exposure of the developing CNS. Recently, many laboratories have identified several immediate, as well as long-lasting, epigenetic modifications of DNA methylation, DNA-associated histone proteins and microRNA (miRNA) biogenesis by using a variety of epigenetic approaches in rodent FASD models. Because DNA methylation patterns, DNA-associated histone protein modifications and miRNA-regulated gene expression are crucial for synaptic plasticity and learning and memory, they can therefore offer an answer to many of the neurobehavioral abnormalities that are found in FASD. In this review, we briefly discuss the current literature of DNA methylation, DNA-associated histone proteins modification and miRNA and review recent developments concerning epigenetic changes in FASD. Full article

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Open AccessReview

Propofol-Induced Neurotoxicity in the Fetal Animal Brain and Developments in Modifying These Effects—An Updated Review of Propofol Fetal Exposure in Laboratory Animal Studies

by Ming Xiong, Li Zhang, Jing Li, Jean Eloy, Jiang Hong Ye and Alex Bekker

Brain Sci. 2016, 6(2), 11; https://doi.org/10.3390/brainsci6020011 - 28 Mar 2016

Cited by 13 | Viewed by 4999

Abstract

In the past twenty years, evidence of neurotoxicity in the developing brain in animal studies from exposure to several general anesthetics has been accumulating. Propofol, a commonly used general anesthetic medication, administered during synaptogenesis, may trigger widespread apoptotic neurodegeneration in the developing brain [...] Read more.

In the past twenty years, evidence of neurotoxicity in the developing brain in animal studies from exposure to several general anesthetics has been accumulating. Propofol, a commonly used general anesthetic medication, administered during synaptogenesis, may trigger widespread apoptotic neurodegeneration in the developing brain and long-term neurobehavioral disturbances in both rodents and non-human primates. Despite the growing evidence of the potential neurotoxicity of different anesthetic agents in animal studies, there is no concrete evidence that humans may be similarly affected. However, given the growing evidence of the neurotoxic effects of anesthetics in laboratory studies, it is prudent to further investigate the mechanisms causing these effects and potential ways to mitigate them. Here, we review multiple studies that investigate the effects of in utero propofol exposure and the developmental agents that may modify these deleterious effects. Full article

(This article belongs to the Special Issue Neurodegeneration in Developmental and Neoplastic Disorders of the Nervous System)

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Brain Sci., Volume 6, Issue 2 (June 2016) – 9 articles

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