https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45189 In situ hybridisation revealed that polyI:C offspring had: (1) SST mRNA reductions in the cingulate cortex and nucleus accumbens shell, regardless of MIA timing; (2) SSTR2 mRNA reductions in the cortex and striatum of GD19, but not GD10, MIA; (3) no alterations in cortical or striatal GAD1 mRNA of polyI:C offspring, but an expected reduction of PVALB mRNA in the infralimbic cortex, and; (4) no alterations in inhibitory markers in hippocampus. Maternal IL-6 response negatively correlated with adult offspring SST mRNA in cortex and striatum, but not hippocampus. These results show lasting inhibitory-related deficits in cortex and striatum in adult offspring from MIA. SST downregulation in specific cortical and striatal subregions, with additional deficits in somatostatin-related signalling through SSTR2, may contribute to some of the adult behavioural changes resulting from MIA and its timing.]]> Wed 26 Oct 2022 14:26:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47091 Wed 14 Dec 2022 09:37:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8286 Sat 24 Mar 2018 08:40:28 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19034 Sat 24 Mar 2018 08:05:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29401 KCNH2. Variable patient responses and a wide range of side effects, however, limit their efficacy. Slow metabolizer status and gene variants in KCNH2 associated with increased expression of Kv11.1-3.1, an alternatively spliced isoform of Kv11.1, are correlated with improved responses to antipsychotic medications. Here, the authors test the hypothesis that these effectsmaybeinfluencedby differential drug binding to Kv11.1 channel isoforms. Method: Drug block of Kv11.1 isoforms was tested in cellular electrophysiology assays. The effects of drug metabolism and KCNH2 genotypes on clinical responses were assessed in patients enrolled in the multicenter Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Results: Risperidone caused greater in vitro block of the alternatively spliced Kv11.1-3.1 isoform than full-length Kv11.1-1A channels, whereas its metabolite paliperidone and other atypical antipsychotics have similar potencies for the two isoforms. In the CATIE study (N=362), patients with genotypes associated with increased Kv11.1-3.1 expression (N=52) showed a better treatment response to risperidone compared with other drugs, but this association was dependent on metabolism status. Patients with KCNH2 risk genotypes and slow metabolizer status (approximately 7% of patients) showed marked improvement in symptoms when treated with risperidone compared with patients with fast metabolizer status or without the KCNH2 risk genotypes. Conclusions: These data support the hypothesis that Kv11.1 channels play a role in the therapeutic action of antipsychotic drugs, particularly risperidone, and further highlight the promise of optimizing response with genotype-guided therapy for schizophrenia patients.]]> Sat 24 Mar 2018 07:36:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48732 Fri 31 Mar 2023 09:37:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46105 Fri 11 Nov 2022 11:44:05 AEDT ]]>