| NT3 |
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| 1 | | Med. Hypotheses 2002 Aug 59: 154-8 |
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| PMID | 12208201 |
| Title | Schizophrenia and other mental disorders require long-term adoptive immunotherapy. |
| Abstract | Many different microbial factors seem to contribute to the pathogenesis of schizophrenic and other psychiatric disorders. Activation of all T lymphocytes reactivates those downregulated by low-grade chronic infections and restores equilibrium in immune cell subpopulations. Different immune cell subpopulations express different neurotrophin receptors and produce different cytokines, particularly brain-derived neurotrophin (BDNF) and neurotrophin 3 (NT3) [M. Besser, R. Wank, J. Immunol. 162 (1998) 6303-6306] that appear to play a key role in schizophrenic and bipolar disorders [E. Jonsson, S. Brene, X.R. Zhang, et al., Acta Psychiatr. Scand. 95 (1997) 414-419; R.S. Duman, Arch. Gen. Psychiatry 54 (1997) 597-606; J.A. Siuciak, D.R. Lewis, S.J. Wiegand, R.M. Lindsay, Pharmacol. Biochem. Be 56 (1997) 131-137]. The hypothesis that adoptive immunotherapy is effective in psychiatric disorders will be supported by three case reports, in a patient with bipolar disorder, a patient with schizophrenia, and a patient with autism. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 2 | | Med. Hypotheses 2002 Aug 59: 154-8 |
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| PMID | 12208201 |
| Title | Schizophrenia and other mental disorders require long-term adoptive immunotherapy. |
| Abstract | Many different microbial factors seem to contribute to the pathogenesis of schizophrenic and other psychiatric disorders. Activation of all T lymphocytes reactivates those downregulated by low-grade chronic infections and restores equilibrium in immune cell subpopulations. Different immune cell subpopulations express different neurotrophin receptors and produce different cytokines, particularly brain-derived neurotrophin (BDNF) and neurotrophin 3 (NT3) [M. Besser, R. Wank, J. Immunol. 162 (1998) 6303-6306] that appear to play a key role in schizophrenic and bipolar disorders [E. Jonsson, S. Brene, X.R. Zhang, et al., Acta Psychiatr. Scand. 95 (1997) 414-419; R.S. Duman, Arch. Gen. Psychiatry 54 (1997) 597-606; J.A. Siuciak, D.R. Lewis, S.J. Wiegand, R.M. Lindsay, Pharmacol. Biochem. Be 56 (1997) 131-137]. The hypothesis that adoptive immunotherapy is effective in psychiatric disorders will be supported by three case reports, in a patient with bipolar disorder, a patient with schizophrenia, and a patient with autism. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 3 | | Schizophr. Res. 2004 Dec 71: 353-60 |
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| PMID | 15474906 |
| Title | Meta-analyses of the association between genetic polymorphisms of neurotrophic factors and schizophrenia. |
| Abstract | Based on the neurodevelopmental hypothesis of schizophrenia, neurotrophic factors (NTFs) may be involved in its pathogenesis. Previous association studies between schizophrenia and neurotrophic factors have shown inconsistent results, which might be due to the heterogeneity and small sample size of the studies. To reach a conclusive understanding of the association, we used a meta-analytic method to study the association of schizophrenia with the polymorphisms in two candidate genes, ciliary neurotrophic factor (CNTF) and neurotrophin 3 (NT3). In our study, two meta-analyses were performed. One included eight studies examining the association of schizophrenia with the A3 allele in a dinucleotide repeat polymorphism of the NT3 gene promoter (N=1938). The other was employed in nine studies examining the association with a null mutation of the CNTF gene (N=2393). Neither of these analyses provided evidence for association. However, our sub-analyses showed a trend of association between the NT3 polymorphism and schizophrenics in Japanese, as well as an association between the CNTF null mutation and schizophrenics without psychiatric family history. These results suggested that the variations at the NT3 and the CNTF genes do not influence the schizophrenia risk, but a role in the susceptibility of subgroups of the patients cannot be excluded. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 4 | | Schizophr. Res. 2004 Dec 71: 353-60 |
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| PMID | 15474906 |
| Title | Meta-analyses of the association between genetic polymorphisms of neurotrophic factors and schizophrenia. |
| Abstract | Based on the neurodevelopmental hypothesis of schizophrenia, neurotrophic factors (NTFs) may be involved in its pathogenesis. Previous association studies between schizophrenia and neurotrophic factors have shown inconsistent results, which might be due to the heterogeneity and small sample size of the studies. To reach a conclusive understanding of the association, we used a meta-analytic method to study the association of schizophrenia with the polymorphisms in two candidate genes, ciliary neurotrophic factor (CNTF) and neurotrophin 3 (NT3). In our study, two meta-analyses were performed. One included eight studies examining the association of schizophrenia with the A3 allele in a dinucleotide repeat polymorphism of the NT3 gene promoter (N=1938). The other was employed in nine studies examining the association with a null mutation of the CNTF gene (N=2393). Neither of these analyses provided evidence for association. However, our sub-analyses showed a trend of association between the NT3 polymorphism and schizophrenics in Japanese, as well as an association between the CNTF null mutation and schizophrenics without psychiatric family history. These results suggested that the variations at the NT3 and the CNTF genes do not influence the schizophrenia risk, but a role in the susceptibility of subgroups of the patients cannot be excluded. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 5 | | Neurosci. Lett. 2008 Aug 440: 197-201 |
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| PMID | 18572319 |
| Title | Decreased serum neurotrophin 3 in chronically medicated schizophrenic males. |
| Abstract | There is evidence that major psychiatric disorders such as schizophrenia (SZ) are associated with deregulation of synaptic plasticity with downstream alterations of neurotrophins. NT3 is an important neurotrophin in the central nervous system, and performs key biological functions, such as promoting the survival, differentiation, and plasticity of neurons. NT3 has a central role in the early neuronal development; enhancing the survival of dopaminergic neurons, suggesting possible involvement in the physiopathology of dopamine related neuropsychiatric disorders such as SZ. Variations in the NT3 gene increase the risk of SZ. Three groups of chronically medicated DSM-IV patients with SZ, on treatment with clozapine (n=12), haloperidol (n=12), risperidone (n=12) and 10 healthy controls had 5 ml blood samples collected by venipuncture. NT3 serum levels were assessed using sandwich-ELISA and were significantly lower in SZ patients (p<0.005) when compared to either controls. These findings suggest that the NT3 signaling system may play a role in the pathophysiology of SZ and might be related to the course of illness or to treatment variables. Longitudinal studies are warranted. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 6 | | Neurosci. Lett. 2008 Aug 440: 197-201 |
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| PMID | 18572319 |
| Title | Decreased serum neurotrophin 3 in chronically medicated schizophrenic males. |
| Abstract | There is evidence that major psychiatric disorders such as schizophrenia (SZ) are associated with deregulation of synaptic plasticity with downstream alterations of neurotrophins. NT3 is an important neurotrophin in the central nervous system, and performs key biological functions, such as promoting the survival, differentiation, and plasticity of neurons. NT3 has a central role in the early neuronal development; enhancing the survival of dopaminergic neurons, suggesting possible involvement in the physiopathology of dopamine related neuropsychiatric disorders such as SZ. Variations in the NT3 gene increase the risk of SZ. Three groups of chronically medicated DSM-IV patients with SZ, on treatment with clozapine (n=12), haloperidol (n=12), risperidone (n=12) and 10 healthy controls had 5 ml blood samples collected by venipuncture. NT3 serum levels were assessed using sandwich-ELISA and were significantly lower in SZ patients (p<0.005) when compared to either controls. These findings suggest that the NT3 signaling system may play a role in the pathophysiology of SZ and might be related to the course of illness or to treatment variables. Longitudinal studies are warranted. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 7 | | Eur Arch Psychiatry Clin Neurosci 2010 Mar 260: 151-62 |
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| PMID | 19579000 |
| Title | Risperidone and haloperidol promote survival of stem cells in the rat hippocampus. |
| Abstract | Altered neuroplasticity contributes to the pathophysiology of schizophrenia. However, the idea that antipsychotics may act, at least in part, by normalizing neurogenesis has not been consistently supported. Our study seeks to determine whether hippocampal cell proliferation is altered in adult rats pretreated with ketamine, a validated model of schizophrenia, and whether chronic administration with neuroleptic drugs (haloperidol and risperidone) affect changes of cell genesis/survival. Ketamine per se has no effect on cell proliferation. Its withdrawal, however, significantly induced cell proliferation/survival in the hippocampus. Risperidone and haloperidol supported cell genesis/survival as well. During ketamine withdrawal, however, their application did not affect cell proliferation/survival additionally. TUNEL staining indicated a cell-protective potency of both neuroleptics with respect to a ketamine-induced cell death. As RT-PCR and Western blot revealed that the treatment effects of risperidone and haloperidol seemed to be mediated through activation of VEGF and MMP2. The mRNA expression of NGF, BDNF, and NT3 was unaffected. From the respective receptors, only TrkA was enhanced when ketamine withdrawal was combined with risperidone or haloperidol. Risperidone also induced BCL-2. Ketamine withdrawal has no effect on the expression of VEGF, MMP2, or BCL-2. It activated the expression of BDNF. This effect was normalized by risperidone or haloperidol. The findings indicate a promoting effect of risperidone and haloperidol on survival of young neurons in the hippocampus by enhancing the expression of the anti-apoptotic protein BCL-2 and by activation of VEGF/MMP2, whereby an interference with ketamine and thus a priority role of the NMDA system was not evident. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |
| 8 | | Neuroimage 2013 Nov 82: 146-53 |
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| PMID | 23727532 |
| Title | Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults. |
| Abstract | The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain. To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6 ± 2.2 years; range: 20-29 years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity. FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics |