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Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine

Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine
Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine
Growing genetic evidence has implicated a role for neuregulin-1 (NRG-1) in schizophrenia pathogenesis as well as alterations in SNAP receptor (SNARE) proteins at both gene and protein levels in post-mortem investigations. In relation to a potential therapeutic mechanism for atypical antipsychotic medications, clozapine has been shown to increase both NRG-1 levels and synaptic markers in rodents. As evidence continues to mount for a potential restoration in connectivity by antipsychotic medications being a mode of efficacy we chose to examine the effects of the atypical antipsychotic clozapine and the typical antipsychotic haloperidol on NRG-1 and SNARE protein transcripts in human brain aggregates exposed to plasma levels chronically for a period of three weeks. At the end of this exposure period we performed quantitative real-time PCR to investigate the mRNA levels of NRG-1, VAMP-1 and SNAP-25. Overall we found that clozapine had the ability to upregulate NRG-1 (+3.58 fold change) and VAMP-1 (+1.92) while SNAP-25 remained unchanged. Changes for haloperidol exposed aggregates were below our cut-off of +1.5. Overall the results of our investigation lend further support to atypical antipsychotic medications having the potential to increase levels of neurotrophic and synaptic markers such as NRG-1 and VAMP-1, the former being a strong candidate susceptibility gene for schizophrenia. In the absence of frank neuronal loss in schizophrenia, restoration of neuronal and synaptic functions by atypical antipsychotics in the brains of schizophrenics maybe a key mechanism of therapeutic efficacy by re-establishing normal connectivity and functioning.
0920-9964
273-276
Chana, G.
166cf442-9374-499a-9be9-6d1666793241
Lucero, G.
9d18bd27-4211-418e-a7cd-c36fad6b3b01
Salaria, S.
ff04a077-68f3-4148-b4a8-ff42a46ac6fe
Lozach, J.
22cca36d-edb9-479c-87e2-0924423d80eb
Du, P.
69536198-13c6-4220-a12d-f1cb5daa383b
Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Everall, I.
6457dfaa-b6c8-4e61-9310-4a9bc5f610ff
Chana, G.
166cf442-9374-499a-9be9-6d1666793241
Lucero, G.
9d18bd27-4211-418e-a7cd-c36fad6b3b01
Salaria, S.
ff04a077-68f3-4148-b4a8-ff42a46ac6fe
Lozach, J.
22cca36d-edb9-479c-87e2-0924423d80eb
Du, P.
69536198-13c6-4220-a12d-f1cb5daa383b
Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Everall, I.
6457dfaa-b6c8-4e61-9310-4a9bc5f610ff

Chana, G., Lucero, G., Salaria, S., Lozach, J., Du, P., Woelk, C.H. and Everall, I. (2009) Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine. Schizophrenia Research, 113 (2-3), 273-276. (doi:10.1016/j.schres.2009.05.015). (PMID:19502011)

Record type: Article

Abstract

Growing genetic evidence has implicated a role for neuregulin-1 (NRG-1) in schizophrenia pathogenesis as well as alterations in SNAP receptor (SNARE) proteins at both gene and protein levels in post-mortem investigations. In relation to a potential therapeutic mechanism for atypical antipsychotic medications, clozapine has been shown to increase both NRG-1 levels and synaptic markers in rodents. As evidence continues to mount for a potential restoration in connectivity by antipsychotic medications being a mode of efficacy we chose to examine the effects of the atypical antipsychotic clozapine and the typical antipsychotic haloperidol on NRG-1 and SNARE protein transcripts in human brain aggregates exposed to plasma levels chronically for a period of three weeks. At the end of this exposure period we performed quantitative real-time PCR to investigate the mRNA levels of NRG-1, VAMP-1 and SNAP-25. Overall we found that clozapine had the ability to upregulate NRG-1 (+3.58 fold change) and VAMP-1 (+1.92) while SNAP-25 remained unchanged. Changes for haloperidol exposed aggregates were below our cut-off of +1.5. Overall the results of our investigation lend further support to atypical antipsychotic medications having the potential to increase levels of neurotrophic and synaptic markers such as NRG-1 and VAMP-1, the former being a strong candidate susceptibility gene for schizophrenia. In the absence of frank neuronal loss in schizophrenia, restoration of neuronal and synaptic functions by atypical antipsychotics in the brains of schizophrenics maybe a key mechanism of therapeutic efficacy by re-establishing normal connectivity and functioning.

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Published date: September 2009
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 352812
URI: https://eprints.soton.ac.uk/id/eprint/352812
ISSN: 0920-9964
PURE UUID: 2c387716-76a6-49b4-ad20-fe37b810f14e

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Date deposited: 21 May 2013 11:59
Last modified: 18 Jul 2017 04:11

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