Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex

Colantuoni, Carlo; Hyde, Thomas M.; Mitkus, Shruti N.; Joseph, Andrew; Sartorius, Leah; Aguirre, Claudia; Creswell, Johanna; Johnson, Elizabeth; Deep-Soboslay, Amy; Herman, Mary M.; Lipska, Barbara K.; Weinberger, Daniel R.; Kleinman, Joel E.

doi:10.1007/s00429-008-0188-y

Cited by 19 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of particular note are four genes -RELN, RGS4, ERBB3 and GSK3B -whose expression was downregulated in ONS cells from SZ patients. There is consistent and repeatable evidence that gene and protein expression of these four genes are downregulated in post-mortem brain from SZ patients (Impagnatiello et al, 1998;Guidotti et al, 2000;Kozlovsky et al, 2000;Fatemi et al, 2001;Hakak et al, 2001;Mirnics et al, 2001;Aston et al, 2004;Kozlovsky et al, 2004;Erdely et al, 2006;Colantuoni et al, 2008). Several of these genes are involved in highly inter-related signalling pathways in which other genes are affected.…”

Section: Ons Cells As a Model For Szmentioning

confidence: 75%

Disease-specific, neurosphere-derived cells as models for brain disorders

Matigian

Abrahamsen

Sutharsan

et al. 2010

Disease Models &Amp; Mechanisms

187

237

View full text Add to dashboard Cite

SUMMARYThere is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.

show abstract

Section: Ons Cells As a Model For Szmentioning

confidence: 75%

Disease-specific, neurosphere-derived cells as models for brain disorders

Matigian

Abrahamsen

Sutharsan

et al. 2010

Disease Models &Amp; Mechanisms

187

237

View full text Add to dashboard Cite

show abstract

“…1,2 Although initial trials with mGluR2/3 agonists have had mixed results, [3][4][5][6][7] data increasingly indicate that changes in mGluR3 are associated with schizophrenia and aging, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] encouraging this treatment strategy. Clinical trials were originally based on data from rodent models.…”

Section: Introductionmentioning

confidence: 99%

“…dlPFC function declines with age in both humans and monkeys, including age-related reductions in persistent neuronal firing because of disinhibited cAMP-potassium channel signaling and spine loss. 36,37 Interestingly, mGluR2/3 expression decreases with advancing age in human dlPFC, 22 suggesting that reduced mGluR2/3 actions may contribute to disinhibited cAMP signaling and age-related cognitive decline.…”

Section: Introductionmentioning

confidence: 99%

mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions

et al. 2017

View full text Add to dashboard Cite

“…In a particularly intriguing example, Niwa et al 45 reported that a transient knockdown of DISC1 in the frontal cortex in the pre-and perinatal mouse brain led to neurochemical and behavioural disruptions emerging in early adulthood. Moreover, some of the vulnerability alleles of candidate genes, such as NRG1 and DISC1, seem to selectively influence splice variants expressed predominantly in developing cortex, implicating isoforms that show large developmental changes in expression in the prefrontal cortex [46][47][48] . As a final link to development, the genetics of schizophrenia overlaps with the genetics of autism and other neurodevelopmental disorders 19,49 .…”

Section: Mapping the Pathophysiology Of Schizophreniamentioning

confidence: 99%