| 1 | Brain Res. Mol. Brain Res. 2002 Nov 107: 190-4 |
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| PMID | 12425947 |
| Title | Decreased hyperlocomotion induced by MK-801, but not amphetamine and caffeine in mice lacking cellular prion protein (PrP(C)). |
| Abstract | The cellular prion protein (PrP(C)) has been involved in several neurodegenerative disorders however it has been proposed that it is also be implicated in psychotic disorders. We investigated the effect of three psychotropic drugs in locomotor activity of PrP(C) knockout (PRNP(O/O)) and wild-type mice. The NMDA receptor channel blocker MK-801 (0.25 mg/kg), the indirect dopamine agonist amphetamine (1 mg/kg) and the adenosine receptor antagonist caffeine (10 mg/kg) were administered i.p. after 60 min of habituation and locomotion was monitored for 3 h. PRNP(O/O) mice presented a diminished hyperlocomotor response to MK-801 treatment but normal response to amphetamine and caffeine compared to wild type mice. These results suggest that lack of PrP(C) leads to a functional alteration in the glutamatergic system, whereas the regulation of both dopaminergic and adenosinergic systems are preserved. Finally, lack of PrP(C) seems not to exacerbate the response to these psychotropic drugs, which modulate neurotransmitter systems possibly involved in schizophrenia and psychotic disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Neuroimage 2002 Jan 15: 200-6 |
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| PMID | 11771989 |
| Title | Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments in healthy volunteers and schizophrenic patients. |
| Abstract | Twin studies point toward a substantial heritability in individual variations in the size of the human brain. However, the etiology is largely unknown. The prion protein (gene name: PRNP) aids cellular resistance to oxidative stress and neurodegeneration and is involved in neurodevelopment. This study examines the influence of a polymorphism in the PRNP gene on brain morphology in 47 healthy males and 43 male schizophrenic patients. All subjects underwent identical MRI scanning sessions followed by segmentation in cerebrospinal fluid (CSF), gray and white matter tissue, and genotyping for a biallelic polymorphism in PRNP (Met129Val). Genotype and allele frequencies did not differ between schizophrenic patients and controls but the polymorphism was associated with white matter tissue reduction (P = 0.024) and enlargement of CSF compartments (P = 0.039). These findings suggest that homozygosity for methionine at codon 129 is associated with decreased white matter tissue and larger CSF volume in right-handed male healthy volunteers and schizophrenic patients. This, however, being a novel finding, should warrant further investigation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Acta Neuropathol. 2003 Jul 106: 92-6 |
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| PMID | 12682740 |
| Title | Neuropathological features of a case with schizophrenia and prion protein gene P102L mutation before onset of Gerstmann-Sträussler-Scheinker disease. |
| Abstract | Gerstmann-Sträussler-Scheinker disease (GSS) is a hereditary transmissible spongiform encephalopathy associated with prion protein gene mutation P102L. The age of onset is roughly restricted to around the sixth decade; however, it is unclear whether the disease-specific pathology of GSS is already evident in the pre-clinical stage. We had a chance to examine an autopsy case with PRNP P102L mutation. The patient had died at 50 years of age before the clinical symptoms of GSS had appeared; neither neuronal loss, gliosis nor spongiform change was found anywhere in the brain. Immunohistochemistry failed to detect any deposition of prion protein. It is thus considered that amyloid plaque formation in GSS probably develops in a relatively rapid fashion compared with Alzheimer's disease. Although the patient suffered from schizophrenia, no significant pathological changes were detected except for astrocytic inclusion bodies in the cerebral cortex. The nature and significance of the inclusion bodies, which are not observed in patients with GSS, remain unclear. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Dis. Markers 2010 -1 28: 315-21 |
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| PMID | 20592456 |
| Title | Lack of association between PRNP M129V polymorphism and multiple sclerosis, mild cognitive impairment, alcoholism and schizophrenia in a Korean population. |
| Abstract | The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases. In this study, we examined the possible genetic association of PRNP*129Val with multiple sclerosis (MS, n=681), mild cognitive impairment (MCI, n=801), alcoholism (n=761) and schizophrenia (n=715) in a Korean population, and compared the data with previous genetic association studies of the variant. The minor allele frequency of PRNP*129Val (MAF =0.025) was significantly lower in Korean population (n=2,479) compared to Caucasian populations (P < 0.0001), suggestive of a weak influence of the variant in the previous population. Statistical analysis revealed no significant association between PRNP*129Val and MS (P= 0.76), MCI (P=0.46), alcoholism (P=0.84) and schizophrenia (P =0.69). These findings were discussed in the context of prior inconsistent reports on the role of PRNP*129Val polymorphism in several diseases. Results from this study may provide further evidence that PRNP M129V is not a genetic susceptibility factor for MS, MCI, alcoholism and schizophrenia in a Korean population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Neurol. Sci. 2014 Feb 35: 239-44 |
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| PMID | 24091711 |
| Title | Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy. |
| Abstract | The cellular prion protein, encoded by PRNP gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the PRNP was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the PRNP gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The PRNP coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal PRNP genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the PRNP variant alleles. The presence of PRNP variant allele at codon 129 was not associated with the analyzed cerebellum volume. PRNP variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Neuropsychiatr Dis Treat 2015 -1 11: 2315-22 |
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| PMID | 26396515 |
| Title | Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family. |
| Abstract | Alzheimer's disease (AD) is the most common form of dementia, which can be categorized into two main forms: early onset AD and late onset AD. The genetic background of early onset AD is well understood, and three genes, the APP, PSEN1, and PSEN2 have been identified as causative genes. In the current study, we tested three siblings from Malaysia who were diagnosed with early onset dementia, as well as their available family members. The family history was positive as their deceased father was similarly affected. Patients were tested for mutations in APP, PSEN1, PSEN2, and PRNP. A novel variant, E280K, was discovered in exon 8 of PSEN1 in the three siblings. In silico analyses with SIFT, SNAP, and PolyPhen2 prediction tools and three-dimensional modeling were performed, and the results suggested that the mutation is probably a pathogenic variant. Two additional pathogenic mutations were previously been described for codon 280, E280A, and E280G, which could support the importance of the E280 residue in the PS1 protein contributing to the pathogenic nature of E280K. Additional ten family members were screened for the E280K mutation, and all of them were negative. Six of them presented with a variety of neuropsychiatric symptoms, including learning disabilities, epilepsy, and schizophrenia, while four family members were asymptomatic. A novel PRNP G127S mutation was found in a step-niece of the three siblings harboring the PSEN1 E280K mutation. In silico predictions for PRNP G127S mutation suggested that this might be possibly a damaging variant. Additional studies to characterize PRNP G127S would be necessary to further understand the effects of this mutation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Neurobiol. Aging 2015 May 36: 2004.e1-8 |
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| PMID | 25726360 |
| Title | Rare structural genetic variation in human prion diseases. |
| Abstract | Prion diseases are a diverse group of neurodegenerative conditions, caused by the templated misfolding of prion protein. Aside from the strong genetic risk conferred by multiple variants of the prion protein gene (PRNP), several other variants have been suggested to confer risk in the most common type, sporadic Creutzfeldt-Jakob disease (sCJD) or in the acquired prion diseases. Large and rare copy number variants (CNVs) are known to confer risk in several related disorders including Alzheimer's disease (at APP), schizophrenia, epilepsy, mental retardation, and autism. Here, we report the first genome-wide analysis for CNV-associated risk using data derived from a recent international collaborative association study in sCJD (n = 1147 after quality control) and publicly available controls (n = 5427). We also investigated UK patients with variant Creutzfeldt-Jakob disease (n = 114) and elderly women from the Eastern Highlands of Papua New Guinea who proved highly resistant to the epidemic prion disease kuru, who were compared with healthy young Fore population controls (n = 395). There were no statistically significant alterations in the burden of CNVs >100, >500, or >1000 kb, duplications, or deletions in any disease group or geographic region. After correction for multiple testing, no statistically significant associations were found. A UK blood service control sample showed a duplication CNV that overlapped PRNP, but these were not found in prion disease. Heterozygous deletions of a 3' region of the PARK2 gene were found in 3 sCJD patients and no controls (p = 0.001, uncorrected). A cell-based prion infection assay did not provide supportive evidence for a role for PARK2 in prion disease susceptibility. These data are consistent with a modest impact of CNVs on risk of late-onset neurologic conditions and suggest that, unlike APP, PRNP duplication is not a causal high-risk mutation. |
| SCZ Keywords | schizophrenia, schizophrenic |