Patrizia Casaccia

Bio: Patrizia Casaccia is an academic researcher from City University of New York. The author has contributed to research in topics: Oligodendrocyte & Myelin. The author has an hindex of 39, co-authored 106 publications receiving 5179 citations. Previous affiliations of Patrizia Casaccia include Rutgers University & Icahn School of Medicine at Mount Sinai.

Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models.

Abstract: The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.

Impaired adult myelination in the prefrontal cortex of socially isolated mice.

Abstract: Protracted social isolation of adult mice induced behavioral, transcriptional and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC) and impaired adult myelination. Social re-integration was sufficient to normalize behavioral and transcriptional changes. Short periods of isolation affected chromatin and myelin, but did not induce behavioral changes. Thus, myelinating oligodendrocytes in the adult PFC respond to social interaction with chromatin changes, suggesting that myelination acts as a form of adult plasticity.

Brain Cell Type Specific Gene Expression and Co-expression Network Architectures

Abstract: Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA expression data sets that were generated within the past several years. We defined three measures of brain cell type-relative expression including specificity, enrichment, and absolute expression and identified corresponding consensus brain cell “signatures,” which were well conserved across data sets. We validated that the relative expression of top cell type markers are associated with proxies for cell type proportions in bulk RNA expression data from postmortem human brain samples. We further validated novel marker genes using an orthogonal ATAC-seq dataset. We performed multiscale coexpression network analysis of the single cell data sets and identified robust cell-specific gene modules. To facilitate the use of the cell type-specific genes for cell type proportion estimation and deconvolution from bulk brain gene expression data, we developed an R package, BRETIGEA. In summary, we identified a set of novel brain cell consensus signatures and robust networks from the integration of multiple datasets and therefore transcend limitations related to technical issues characteristic of each individual study.

Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains

Abstract: Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis-affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis-affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis-affected brains.

Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

Abstract: A combination of genes and environmental factors underlie an individual’s risk of developing a mental illness. Among the environmental factors, it is becoming clear that communication between the gut and the brain is involved, but we do not understand how these two organs communicate. Our gut contains a variety of bacteria that help us to digest food and there is some evidence that changes in these bacterial communities can influence our mental health. Transplanting feces from one individual to the gut of another is one way to alter the communities of bacteria in the gut. Here, Gacias et al. investigated whether fecal transplants are sufficient to induce social avoidance behavior – a symptom of depression – in mice. The experiments show that introducing specific combinations of bacteria into the gut is indeed able to cause healthy adult mice to avoid social interactions. This effect was caused by changes in the “myelin” sheath that surrounds many nerve fibers and could be prevented by giving the mice antibiotics, which decreased the number of bacteria in the gut. Further experiments revealed that the mice that became depressed after fecal transplants had higher levels of a molecule called cresol, which is produced by certain gut bacteria. Gacias et al. found that cresol is able to reduce the amount of myelin produced by brain cells. Therefore, these findings show that changing the communities of bacteria in the gut can result in the accumulation of molecules that influence social behavior. Future work will aim to identify bacteria that can reduce the amount of cresol produced in the gut, which may have the potential to treat depression.

Adverse Health Effects of Marijuana Use

Abstract: As marijuana use becomes legal in some states, the dominant public opinion is that marijuana is a harmless source of mood alteration. Although the harms associated with marijuana use have not been well studied, enough information is available to cause concern.

The Microbiota-Gut-Brain Axis

Abstract: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

Abstract: The GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotrans

Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain

Abstract: Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity-regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.

TET-mediated active DNA demethylation: mechanism, function and beyond

Abstract: A key mode of regulating DNA methylation is through active demethylation driven by TET-mediated oxidation of 5-methylcytosine (5mC). This Review discusses our latest understanding of the mechanisms and regulation of active DNA demethylation, and the roles of active demethylation (and the oxidized 5mC intermediates) in gene regulation, genome stability, development and disease.