Dataset Information

Searching for neuropathology: gliosis in schizophrenia.

ABSTRACT: The neuropathology of schizophrenia remains elusive. One indication of this elusiveness is that the literature, in contrast to that on the neuropathology of almost any other disease, deals predominantly with measures of normal structures rather than with the demonstration and characterization of pathological structures. An important exception to this trend has been the continued search, over four decades, for reactive glia. In this article, we review histological and radiological evidence for and against astrocytosis and microgliosis specifically associated with schizophrenia. The studies are generally limited by small samples, flawed designs, and potentially biased methods of counting cells. Interpretation of these studies is further complicated by the frequent presence of glial reactions in older individuals without psychiatric disease. Nonetheless, some of the positive findings in the literature cannot easily be dismissed. A sufficiently large autopsy study, weighted toward younger subjects, could provide a definitive answer, which if positive could be a major step toward finding an underlying pathological process.

SUBMITTER: Schnieder TP

PROVIDER: S-EPMC3593070 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Searching for neuropathology: gliosis in schizophrenia.

Schnieder Tatiana P TP Dwork Andrew J AJ

Biological psychiatry 20101030 2

The neuropathology of schizophrenia remains elusive. One indication of this elusiveness is that the literature, in contrast to that on the neuropathology of almost any other disease, deals predominantly with measures of normal structures rather than with the demonstration and characterization of pathological structures. An important exception to this trend has been the continued search, over four decades, for reactive glia. In this article, we review histological and radiological evidence for an ...[more]

PMID: 21035789

Similar Datasets

Project description:Due to an inability to ethically access developing human brain tissue as well as identify prospective cases, early-arising neurodevelopmental and cell-specific signatures of Schizophrenia (Scz) have remained unknown and thus undefined. To overcome these challenges, we utilized patient-derived induced pluripotent stem cells (iPSCs) to generate 3D cerebral organoids to model neuropathology of Scz during this critical period. We discovered that Scz organoids exhibited ventricular neuropathology resulting in altered progenitor survival and disrupted neurogenesis. This ultimately yielded fewer neurons within developing cortical fields of Scz organoids. Single-cell sequencing revealed that Scz progenitors were specifically depleted of neuronal programming factors leading to a remodeling of cell-lineages, altered differentiation trajectories, and distorted cortical cell-type diversity. While Scz organoids were similar in their macromolecular diversity to organoids generated from healthy controls (Ctrls), four GWAS factors (PTN, COMT, PLCL1, and PODXL) and peptide fragments belonging to the POU-domain transcription factor family (e.g., POU3F2/BRN2) were altered. This revealed that Scz organoids principally differed not in their proteomic diversity, but specifically in their total quantity of disease and neurodevelopmental factors at the molecular level. Single-cell sequencing subsequently identified cell-type specific alterations in neuronal programming factors as well as a developmental switch in neurotrophic growth factor expression, indicating that Scz neuropathology can be encoded on a cell-type-by-cell-type basis. Furthermore, single-cell sequencing also specifically replicated the depletion of BRN2 (POU3F2) and PTN in both Scz progenitors and neurons. Subsequently, in two mechanistic rescue experiments we identified that the transcription factor BRN2 and growth factor PTN operate as mechanistic substrates of neurogenesis and cellular survival, respectively, in Scz organoids. Collectively, our work suggests that multiple mechanisms of Scz exist in patient-derived organoids, and that these disparate mechanisms converge upon primordial brain developmental pathways such as neuronal differentiation, survival, and growth factor support, which may amalgamate to elevate intrinsic risk of Scz.

Dataset Information

Searching for neuropathology: gliosis in schizophrenia.

Publications

Searching for neuropathology: gliosis in schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets