Differential Macrophage Responses in Affective Versus Non-Affective First-Episode Psychosis Patients.

Increased innate immune activation and inflammation are common findings in psychotic and affective (mood) disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), including increased numbers and activation of monocytes and macrophages. These findings often differ depending on the disorder, for example, we previously found increases in circulating inflammatory cytokines associated with monocytes and macrophages in SCZ, while BD had increases in anti-inflammatory cytokines. Despite these differences, few studies have specifically compared immune dysfunction in affective versus non-affective psychotic disorders and none have compared functional monocyte responses across these disorders.

Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are a group of heterogeneous neurological disorders that are highly variable and are clinically characterized by deficits in social interactions, communication, and stereotypical behaviors. Prevalence has risen from 1 in 10,000 in 1972 to 1 in 59 children in the United States in 2014. This rise in prevalence could be due in part to better diagnoses and awareness, however, these together cannot solely account for such a significant rise.

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.

Background: Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases.

Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats.

Unlabelled: Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study.

The subventricular zone continues to generate corpus callosum and rostral migratory stream astroglia in normal adult mice.

Astrocytes are the most abundant cells in the CNS, and have many essential functions, including maintenance of blood-brain barrier integrity, and CNS water, ion, and glutamate homeostasis. Mammalian astrogliogenesis has generally been considered to be completed soon after birth, and to be reactivated in later life only under pathological circumstances. Here, by using genetic fate-mapping, we demonstrate that new corpus callosum astrocytes are continuously generated from nestin(+) subventricular zone (SVZ) neural progenitor cells (NPCs) in normal adult mice.

Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model.

Canavan disease is caused by inactivating ASPA (aspartoacylase) mutations that prevent cleavage of N-acetyl-L-aspartate (NAA), resulting in marked elevations in central nervous system (CNS) NAA and progressively worsening leukodystrophy. We now report that ablating NAA synthesis by constitutive genetic disruption of Nat8l (N-acetyltransferase-8 like) permits normal CNS myelination and prevents leukodystrophy in a murine Canavan disease model.

Enhanced phenotypic alterations of alveolar type II cells in response to Aflatoxin G1 -induced lung inflammation.

Recently, we discovered that Aflatoxin G1 (AFG1 ) induces chronic lung inflammatory responses, which may contribute to lung tumorigenesis in Balb/C mice. The cancer cells originate from alveolar type II cells (AT-II cells). The activated AT-II cells express high levels of MHC-II and COX-2, may exhibit altered phenotypes, and likely inhibit antitumor immunity by triggering regulatory T cells (Tregs).

Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model.

Multiple sclerosis (MS) is characterized by central nervous system (CNS) inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine for CXCR3+ T cells, is known to regulate T cell differentiation and migration in the periphery, but effects of CXCL10 produced endogenously in the CNS on immune cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial CXCL10 synthesis.

Origins and significance of astrogliosis in the multiple sclerosis model, MOG peptide EAE.

Astroglia, the most abundant cells in the human CNS, and even more prominent in multiple sclerosis patients, participate in CNS innate and adaptive immunity, and have been hypothesized to play an important role in multiple sclerosis progression. Experimental autoimmune encephalomyelitis elicited in mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 provides a means by which to explore the genesis and disease significance of astrogliosis during a chronic immune-mediated CNS inflammatory/demyelinative disorder that, in its' pathological features, strongly resembles multiple sclerosis.

Disruption of NMDA receptors in oligodendroglial lineage cells does not alter their susceptibility to experimental autoimmune encephalomyelitis or their normal development.

Pharmacological studies have suggested that oligodendroglial NMDA glutamate receptors (NMDARs) mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), a model of human MS, by timed conditional disruption of oligodendroglial NR1, an essential subunit of functional NMDARs, using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system. We found that selective ablation of oligodendroglial NR1 did not alter the clinical severity of EAE elicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1 KO and non-KO mice in numbers of axons lost in spinal cord dorsal funiculi or severity of spinal cord demyelination.

Macroglial plasticity and the origins of reactive astroglia in experimental autoimmune encephalomyelitis.

Accumulations of hypertrophic, intensely glial fibrillary acidic protein-positive (GFAP(+)) astroglia, which also express immunoreactive nestin and vimentin, are prominent features of multiple sclerosis lesions. The issues of the cellular origin of hypertrophic GFAP(+)/vimentin(+)/nestin(+) "reactive" astroglia and also the plasticities and lineage relationships among three macroglial progenitor populations-oligodendrocyte progenitor cells (OPCs), astrocytes and ependymal cells-during multiple sclerosis and other CNS diseases remain controversial. We used genetic fate-mappings with a battery of inducible Cre drivers (Olig2-Cre-ER(T2), GFAP-Cre-ER(T2), FoxJ1-Cre-ER(T2) and Nestin-Cre-ER(T2)) to explore these issues in adult mice with myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis (EAE).