MedicalResearch.com Interview with:
Brian P. Head, MS, PhD
Associate Professor, UCSD
Research Scientist, VASDHS
Department of Anesthesiology
VA San Diego Healthcare System
San Diego, CA 92161-9125
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia.
SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015).
Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms.
MedicalResearch.com: What should readers take away from your report?
Response: These findings suggest an important role by which neuron-targeted Cav-1 regulates DISC1 neurobiology with implications for synaptic plasticity. Therefore, SynCav1 might be a potential therapeutic target for restoring neuronal function in schizophrenia.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Future direction is to treat human neurons derived from pluripotent stem cells from schizophrenic patients with neuron-targeted caveolin-1 to see if we can reverse the cellular phenotype by regulating DISC1 expression as well as expression of proteins critical for functional synaptic plasticity.
MedicalResearch.com: Is there anything else you would like to add?
Response: We hold a patent with UCSD on the use of the neuron-targeted caveolin-1 expression vector for treating neurodegeneration and mental health disorders.
Here is a link to the patented technology: https://techtransfer.universityofcalifornia.edu/NCD/21446.html
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
J Neurophysiol. 2016 Nov 2:jn.00481.2016. doi: 10.1152/jn.00481.2016. [Epub ahead of print]
Caveolin-1 Regulation of Disrupted-in-Schizophrenia-1 as a Potential Therapeutic Target for Schizophrenia.
Kassan A1, Egawa J, Zhang Z, Almenar-Queralt A, Nguyen QM, Lajevardi Y, Kim K, Posadas E, Jeste DV, Roth DM2, Patel PM2, Patel HH2, Head BP
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