000042372 001__ 42372 000042372 005__ 20240124114341.0 000042372 0247_ $$2doi$$a10.6083/bpxhc42372 000042372 037__ $$aETD 000042372 041__ $$aeng 000042372 245__ $$aDelivering schizophrenia-associated MicroRNA137 to the prefrontal cortex by lipid nanoparticles 000042372 260__ $$bOregon Health and Science University 000042372 269__ $$a2023-12-05 000042372 336__ $$aDissertation 000042372 502__ $$bPh.D. 000042372 502__ $$gBehavioral & Systems Neuroscience 000042372 520__ $$aSchizophrenia (SCZ) is a complex neuropsychiatric disorder thought to arise from an interplay of environmental and genetic risk factors. The presentation of disease symptomology is heterogenous due to the polygenicity of the disorder. The standard antipsychotic drug treatments lack target specificity, have severe side effects, and do not alleviate the most disabling negative and cognitive symptoms. This may be due to a lack of understanding SCZ pathophysiology. Genome-wide association studies (GWAS) identified candidate alleles, largely involved in regulating synaptic function, which confer increased risk for SCZ. The host gene MIR137, contains the primary transcript of microRNA137 (miR137), is strongly implicated in SCZ risk and is associated with more severe psychiatric symptoms. MiR137 regulates tens to hundreds of target transcripts involved in neurodevelopment and synaptic function. Since SCZ is a neurodevelopmental disorder characterized by synaptic dysfunction, miR137 represents an interesting target to modulate protein expression in the prefrontal cortex (PFC), one of the most impacted brain regions. Thus, to improve treatments for people with SCZ, this dissertation investigated the ability of nanoparticles to deliver nucleic acid cargo to the PFC to alter synaptic protein expression. 000042372 536__ $$oNEI$$cR01 EY033423 000042372 536__ $$oNHLBI$$cR01 HL146736 000042372 540__ $$fNo License 000042372 542__ $$fIn copyright - single owner 000042372 650__ $$aNanoparticle Drug Delivery System$$013752 000042372 650__ $$aSchizophrenia$$025757 000042372 650__ $$aMicroRNAs$$034671 000042372 6531_ $$abrain delivery 000042372 6531_ $$aglutamate networks 000042372 6531_ $$alipid nanoparticle 000042372 6531_ $$asynaptic proteins 000042372 691__ $$aSchool of Medicine$$041369 000042372 692__ $$aDepartment of Behavioral Neuroscience$$041394 000042372 7001_ $$aPalumbo, Michelle$$uOregon Health and Science University$$041354$$10000-0003-2910-7170 000042372 711__ $$aNervous System Delivery$$uControlled Release Society$$d2023 000042372 7201_ $$aJanowsky, Aaron$$uOregon Health and Science University$$041354$$eAdvisor$$7Personal 000042372 7201_ $$aAbbas, Atheir$$uOregon Health and Science University$$041354$$eCo-Mentor$$7Personal 000042372 7201_ $$aMarks, Dan$$uOregon Health and Science University$$041354$$eCommittee chair$$7Personal 000042372 7201_ $$aMiranda, Rajesh$$uTexas A & M University$$eCommittee member$$7Personal 000042372 7201_ $$aSahay, Gaurav$$uOregon State University$$eCollaborator$$7Personal 000042372 789__ $$eCites$$whttps://pubmed.ncbi.nlm.nih.gov/37644723/$$2URL 000042372 792__ $$aPalumbo, M.C., Gautam, M., Sonneborn, A., Kim, K., Wilmarth, P.A., Reddy, A.P., Shi, X., Marks, D.L., Sahay, G., Abbas, A.I., Janowsky, A. MicroRNA-137 loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex. Molecular Therapy. S1525-0016(23)00448–3. Oct 4, 2023. 000042372 8564_ $$yChapter 3 publication permission for dissertation$$953bbe7e4-44d3-499d-b917-dabf75bb61c4$$s108552$$uhttps://digitalcollections.ohsu.edu/record/42372/files/MolTher%20Copywrite%20Permission%20Email.pdf 000042372 8564_ $$9d9a41cb4-d326-48cb-8d44-0380988c1281$$s12577383$$uhttps://digitalcollections.ohsu.edu/record/42372/files/Palumbo.Michelle.2023.pdf 000042372 909CO $$ooai:digitalcollections.ohsu.edu:42372$$pstudent-work 000042372 980__ $$aTheses and Dissertations 000042372 981__ $$aPublished$$b2023-12-05