Poster: Neuregulin-1 treatment affects GABA and glutamate release after PCP co-treatment in freely moving mice.

Poster at the annual meeting of the Society for Neuroscience (SfN) 2013, San Diego (USA)

Martin Engel, Andrew Jenner, Xu-Feng Huang, Elisabeth Frank

Background: Evidence from genetic and post-mortem studies strongly supports Neuregulin-1 (NRG1) signalling through ErbB4 to be associated with the pathophysiology of schizophrenia. ErbB4 receptors were found primarily located on GABAergic interneurons in schizophrenia-relevant brain areas, including the hippocampus and prefrontal cortex (PFC). Application of phencyclidine (PCP) has commonly been used to identify compounds with antipsychotic potential. In our previous studies, we showed that acute NRG1 application reduces PCP-induced hyperlocomotion in a dose dependant manner.

Objectives: In the present study we explored the ability of NRG1 to counterbalance PCP-induced alterations of GABA and Glutamate levels in the hippocampus and PFC.

Method: Cerebral spinal fluid samples from the CA1 region of the dorsal hippocampus and PFC of freely moving male C57BL/6 mice were collected via microdialysis. Samples were collected after a 10 min retrodialysis infusion of NRG1 (NRG1β1 EGF Domain; 30 ng/kg), PCP (1 µg/kg), or both. Samples were analysed using advanced gas chromatograph-mass spectrometry (GC-MS/MS) and quantified using calibration standards.

Results: GABA release was significantly increased following PCP application in the hippocampus, but not in the PFC. Co-Administration with NRG1 prevented the PCP-induced GABA level increase in the hippocampus, without effecting release levels in the PFC. NRG1 itself did not alter extracellular GABA in either region. Glutamate release remained fairly unaffected by PCP treatment in both regions.  Following NRG1 treatment, however, reduced glutamate release was observed in the hippocampus and PFC. Following co-administration glutamate remained suppressed in the hippocampus, but not in the PFC.

Conclusion: These results demonstrate the critical role of NRG1 in acute neurotransmission relevant to schizophrenia. With NRG1 application being in a phase II trial for heart disease, our results suggest that NRG1 might also be a potential treatment option for patients with schizophrenia.

Download Poster: Engel et al 2013 SfN Poster

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