Alterations in hippocampal non-phosphorylated MAP2 protein expression in schizophrenia

Cotter, David; Kerwin, Robert; Doshi, Bala; Martin, Carlos Sanchez; Everall, Ian

doi:10.1016/s0006-8993(97)00575-1

Cited by 45 publications

(15 citation statements)

References 39 publications

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“…The mRNA alterations also show that the affected synapses are formed, at least partly, by intrinsic neurons rather than neurons projecting into the hippocampal formation. Thirdly, two studies have found a decrease in dendritic extent and/or dendritic spine density in this region in schizophrenia (Arnold et al, 1991b;Rosoklija et al, 2000), which would be consistent with presynaptic decrements; however, other studies of MAP-2 came to somewhat different conclusions (Cotter et al, 1997(Cotter et al, , 2000.…”

Section: Synaptic and Dendritic Abnormalities In The Hippocampal Formmentioning

confidence: 86%

Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia

Harrison¹,

Eastwood²

2001

Hippocampus

203

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Cytoarchitectural changes in the hippocampal formation have been prominent among the various neuropathological abnormalities reported in schizophrenia. Replicated positive findings include decreased neuronal size and alterations in presynaptic and dendritic markers. These findings, in the absence of neurodegenerative changes, suggest that there are alterations in the neural circuitry in schizophrenia. These may represent the anatomical correlate of the aberrant functional connectivity described in neuroimaging studies, which in turn contributes to the psychotic and cognitive symptomatology of the disorder. The identity of the affected hippocampal circuits remains unclear; there is evidence for both glutamatergic and GABAergic involvement, and perhaps for a gradient of pathology in which changes are most apparent in CA4 and the subiculum, and least in CA1. The data, their interpretation, and their limitations are discussed, with particular emphasis upon molecular and immunological studies of synaptic protein gene expression.

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Section: Synaptic and Dendritic Abnormalities In The Hippocampal Formmentioning

confidence: 86%

Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia

Harrison¹,

Eastwood²

2001

Hippocampus

203

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“…17,20 Several researches have reported that abnormalities of neural cell adhesion, neuronal function, and Wnt/Wingless exist in schizophrenia. [10][11][12][13][14][15]18,19,[23][24][25][26] Third, APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. 27,28 Three SNPs of APC are associated with schizophrenia.…”

Section: Discussionmentioning

confidence: 97%

“…Recently, it has been reported that the mouse tumor suppressor protein APC has a role in acetylcholine receptor clustering and that the Wnt/bcatenin pathway crosstalks with agrin signaling cascade during synapse formation. 22 Hippocampal formation, 23,24 synapse formation, 25 and dysfunction of a prefrontal-hippocampal network 26 are believed to be closely involved in the pathophysiology of schizophrenia. Thus, there might be relationship between the functions of APC and the neural mechanisms underlying schizophrenia.…”

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confidence: 99%

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Cui

Jiang

et al. 2005

Mol Psychiatry

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The etiology of schizophrenia is unclear, although family, twin, and linkage studies implicate genetic factors. Here, we identified adenomatous polyposis coli (APC), a tumor suppressor gene, as a risk factor for schizophrenia. We compared leukocytic gene expression patterns of six pairs of patients with schizophrenia and healthy controls by microarray. APC expression levels were significantly increased in all patients compared to healthy controls. To confirm the findings of microarray analysis, we measured expression levels of APC in the leukocytes from 30 relapse patients taking antipsychotic medication, 29 first-episode drug-naïve patients, and 30 healthy controls using real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). APC expression levels were significantly increased in leukocytes of schizophrenics both taking and not taking antipsychotic medication and hence the increase of APC expression was not due to antipsychotic medication. APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. Further, we performed the transmission disequilibrium test (TDT) and TDT based on haplotypes to search for the association between schizophrenia and APC by examining 163 parent-offspring trios of Chinese descent. We analyzed three single-nucleotide polymorphisms (SNPs) (rs2229992, rs42427, rs465899) at the exon region of APC. TDT showed that the three SNPs are significantly associated with schizophrenia (TDT v 2 ¼ 4.23, Po0.05; 4.15, Po0.05; 8.49 Po0.01, respectively; HHRRv 2 ¼ 5.54, Po0.05; 4.40, Po0.05; 9.79, Po0.01, respectively). We found a significant association between the APC haplotypes from rs2229992-rs42427-rs465899 and schizophrenia (Global v 2 ¼ 44.376,df ¼ 7, Po0.001). The C-A-T haplotype has a frequency of more than 57% and has a strong association with schizophrenia (v 2 ¼ 15.04, Po0.001). These results indicate that the APC may be a candidate gene conferring susceptibility to schizophrenia and also may be associated with reduced vulnerability to cancer in schizophrenia.

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“…The MAPT gene is associated with neurodegenerative diseases such as frontotemporal dementia and Alzheimer disease [Pittman et al, 2006]. There is substantial debate about the involvement of the microtubilin associated proteins in schizophrenia [Arnold et al, 1991;Cotter et al, 1997Cotter et al, , 2000Rioux et al, 2003;Law et al, 2004]. The association of this tau gene with non-affective schizophrenia subjects may suggest that any effect of this gene is more prominent in non-affective subgroups of schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Do mood symptoms subdivide the schizophrenia phenotype? association of the GMP6A gene with a depression subgroup

Boks

Hoogendoorn

Jungerius

et al. 2008

American J of Med Genetics Pt B

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Genetic studies of clinically defined subgroups of schizophrenia patients may reduce the phenotypic heterogeneity of schizophrenia and thus facilitate the identification of genes that confer risk to this disorder. Several latent class analyses have provided subgroups of psychotic disorders that show considerable consistency over these studies. The presence or absence of mood symptoms was found to contribute most to the delineations of these subgroups. In this study we used six previously published subtypes of psychosis derived from latent class analysis of a large sample of psychosis patients. In 280 schizophrenia patients and 525 healthy controls we investigated the associations of these subgroups with myelin related genes. After bonferroni correction we found an association of the glycoprotein M6A gene (GPM6A) with the subgroup of schizophrenia patients with high levels of depression (P-corrected = 0.006). Borderline association of the microtubulin associated protein tau (MAPT) with a primarily non-affective group of schizophrenia patients (P-corrected = 0.052) was also observed. GPM6A modulates the influence of stress on the hippocampus in animals. Thus our findings could suggest that GMP6A plays a role in the stress-induced hippocampal alterations that are found in psychiatric disorders in general and schizophrenia in particular. Overall, these finding suggests that investigating subgroups of schizophrenia based symptoms profile and particularly mood symptoms can facilitate genetic studies of schizophrenia.

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Alterations in hippocampal non-phosphorylated MAP2 protein expression in schizophrenia

Cited by 45 publications

References 39 publications

Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia

Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Do mood symptoms subdivide the schizophrenia phenotype? association of the GMP6A gene with a depression subgroup

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