{"id":{"repo_id":"umn","oai_identifier":"oai:conservancy.umn.edu:11299/191315"},"canonical_url":"https://search.dev.ndltd.org/etd/umn/oai:conservancy.umn.edu:11299/191315","repository":{"repo_id":"umn","name":"University of Minnesota","base_url":"https://conservancy.umn.edu/server/oai/request"},"display":{"title":"Defining a Neuroprotective Pathway for the Treatment of Ataxias","abstract":"Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia caused by neurodegeneration of specific cell types, namely Purkinje Cells (PCs) of the cerebellum. Mouse models of SCA Type 1 (SCA1) can be used to study the molecular mechanisms underlying PC degeneration and death. One SCA1 mouse model, ATXN1[30Q]D776, has an initial ataxia but no progressive degeneration or PC death. RNA-seq experiments identified the up-regulation in the cerebellum of the peptide hormone Cholecystokinin (Cck) in these mice. Knocking out Cck or the Cck1 receptor (Cck1R) in ATXN1[30Q]D776 mice confers a progressive disease where PC death occurs by thirty-six weeks of age. Weighted Gene Co-expression Network Analysis (WGCNA) performed on cerebellar RNA-seq data from ATXN1[30Q]D776;Cck-/- mice identified a disease progression-related gene set named the Pink Module that is influenced by Cck. A Cck1R agonist, A71623, was administered via osmotic minipump to ATXN1[30Q]D776;Cck-/- mice and AXTN1[82Q] mice, which are a more faithful representation of human SCA1 PC degeneration. In both mouse models, A71623 protected against progressive ataxia and PC degeneration. These results suggest that manipulation of the Cck-Cck1R pathway may be a therapeutic target for treatment of diseases involving PC degeneration.","abstract_html":"Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia caused by neurodegeneration of specific cell types, namely Purkinje Cells (PCs) of the cerebellum. Mouse models of SCA Type 1 (SCA1) can be used to study the molecular mechanisms underlying PC degeneration and death. One SCA1 mouse model, ATXN1[30Q]D776, has an initial ataxia but no progressive degeneration or PC death. RNA-seq experiments identified the up-regulation in the cerebellum of the peptide hormone Cholecystokinin (Cck) in these mice. Knocking out Cck or the Cck1 receptor (Cck1R) in ATXN1[30Q]D776 mice confers a progressive disease where PC death occurs by thirty-six weeks of age. Weighted Gene Co-expression Network Analysis (WGCNA) performed on cerebellar RNA-seq data from ATXN1[30Q]D776;Cck-/- mice identified a disease progression-related gene set named the Pink Module that is influenced by Cck. A Cck1R agonist, A71623, was administered via osmotic minipump to ATXN1[30Q]D776;Cck-/- mice and AXTN1[82Q] mice, which are a more faithful representation of human SCA1 PC degeneration. In both mouse models, A71623 protected against progressive ataxia and PC degeneration. These results suggest that manipulation of the Cck-Cck1R pathway may be a therapeutic target for treatment of diseases involving PC degeneration.","abstract_has_math":false,"creators":["Leathley, Emily"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-08","date_published":"2016-08","updated_at":"2026-07-24T05:20:00Z","subjects":["Cerebellum","Cholecystokinin","Neurodegeneration","Purkinje Cell","Spinocerebellar Ataxia","Therapy"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11299/191315","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Leathley, Emily"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-11-27T21:38:01Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2017-11-27T21:38:01Z"]},{"key":"dc:date.issued","label":"Date","values":["2016-08"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cerebellum","Cholecystokinin","Neurodegeneration","Purkinje Cell","Spinocerebellar Ataxia","Therapy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11299/191315"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["University of Minnesota Ph.D. dissertation. August 2016. Major: Neuroscience. Advisor: Harry Orr. 1 computer file (PDF); vii, 100 pages."]},{"key":"dc:description.abstract","label":"Abstract","values":["Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia caused by neurodegeneration of specific cell types, namely Purkinje Cells (PCs) of the cerebellum. Mouse models of SCA Type 1 (SCA1) can be used to study the molecular mechanisms underlying PC degeneration and death. One SCA1 mouse model, ATXN1[30Q]D776, has an initial ataxia but no progressive degeneration or PC death. RNA-seq experiments identified the up-regulation in the cerebellum of the peptide hormone Cholecystokinin (Cck) in these mice. Knocking out Cck or the Cck1 receptor (Cck1R) in ATXN1[30Q]D776 mice confers a progressive disease where PC death occurs by thirty-six weeks of age. Weighted Gene Co-expression Network Analysis (WGCNA) performed on cerebellar RNA-seq data from ATXN1[30Q]D776;Cck-/- mice identified a disease progression-related gene set named the Pink Module that is influenced by Cck. A Cck1R agonist, A71623, was administered via osmotic minipump to ATXN1[30Q]D776;Cck-/- mice and AXTN1[82Q] mice, which are a more faithful representation of human SCA1 PC degeneration. In both mouse models, A71623 protected against progressive ataxia and PC degeneration. These results suggest that manipulation of the Cck-Cck1R pathway may be a therapeutic target for treatment of diseases involving PC degeneration."]},{"key":"dc:title","label":"Title","values":["Defining a Neuroprotective Pathway for the Treatment of Ataxias"]}]}],"canonical_facts":{"dc:creator":["Leathley, Emily"],"dc:date.accessioned":["2017-11-27T21:38:01Z"],"dc:date.available":["2017-11-27T21:38:01Z"],"dc:date.issued":["2016-08"],"dc:description":["University of Minnesota Ph.D. dissertation. August 2016. Major: Neuroscience. Advisor: Harry Orr. 1 computer file (PDF); vii, 100 pages."],"dc:description.abstract":["Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia caused by neurodegeneration of specific cell types, namely Purkinje Cells (PCs) of the cerebellum. Mouse models of SCA Type 1 (SCA1) can be used to study the molecular mechanisms underlying PC degeneration and death. One SCA1 mouse model, ATXN1[30Q]D776, has an initial ataxia but no progressive degeneration or PC death. RNA-seq experiments identified the up-regulation in the cerebellum of the peptide hormone Cholecystokinin (Cck) in these mice. Knocking out Cck or the Cck1 receptor (Cck1R) in ATXN1[30Q]D776 mice confers a progressive disease where PC death occurs by thirty-six weeks of age. Weighted Gene Co-expression Network Analysis (WGCNA) performed on cerebellar RNA-seq data from ATXN1[30Q]D776;Cck-/- mice identified a disease progression-related gene set named the Pink Module that is influenced by Cck. A Cck1R agonist, A71623, was administered via osmotic minipump to ATXN1[30Q]D776;Cck-/- mice and AXTN1[82Q] mice, which are a more faithful representation of human SCA1 PC degeneration. In both mouse models, A71623 protected against progressive ataxia and PC degeneration. These results suggest that manipulation of the Cck-Cck1R pathway may be a therapeutic target for treatment of diseases involving PC degeneration."],"dc:identifier.uri":["http://hdl.handle.net/11299/191315"],"dc:language.iso":["en"],"dc:subject":["Cerebellum","Cholecystokinin","Neurodegeneration","Purkinje Cell","Spinocerebellar Ataxia","Therapy"],"dc:title":["Defining a Neuroprotective Pathway for the Treatment of Ataxias"],"dc:type":["Thesis or Dissertation"]},"updated_at":"2026-07-24T05:20:00Z"}