2023
Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice
Cheng X, Tang Y, Vidyadhara D, Li B, Zimmerman M, Pak A, Nareddula S, Edens P, Chandra S, Chubykin A. Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice. IScience 2023, 26: 107842. PMID: 37766983, PMCID: PMC10520332, DOI: 10.1016/j.isci.2023.107842.Peer-Reviewed Original ResearchParkinson's diseasePyramidal cell synapsesVisual cortical functionSilicon probe recordingsPrimary visual cortexShort-term facilitationFamilial Parkinson's diseaseCortical dysfunctionMotor deficitsMotor symptomsCell synapsesCortical functionRepetitive stimulationVisual cortexOptokinetic responseReleasable poolProlonged stimulationLayer 4Visual responsesMiceSynaptic vesiclesEye movementsOrientation selectivityDysfunctionFunction mutationsDopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease
Vidyadhara D, Somayaji M, Wade N, Yücel B, Zhao H, Shashaank N, Ribaudo J, Gupta J, Lam T, Sames D, Greene L, Sulzer D, Chandra S. Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease. Cell Reports 2023, 42: 112231. PMID: 36920906, PMCID: PMC10127800, DOI: 10.1016/j.celrep.2023.112231.Peer-Reviewed Original ResearchConceptsParkinson's diseaseMotor deficitsDopamine transporterPathogenesis of PDNigral dopaminergic lossProgressive motor deficitsΑ-synuclein pathologyEarly-onset Parkinson's diseaseDopamine sequestrationDopaminergic vulnerabilityDopaminergic lossKO micePresynaptic sitesKO brainNeurochemical analysisDorsal striatumKnockout miceCardinal featuresReuptake kineticsL-DOPADiseaseSynaptic autophagyFunction mutationsDeficitsMiceα-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease
Martin-Lopez E, Vidyadhara D, Liberia T, Meller S, Harmon L, Hsu R, Spence N, Brennan B, Han K, Yücel B, Chandra S, Greer C. α-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease. Journal Of Neuroscience 2023, 43: 1051-1071. PMID: 36596700, PMCID: PMC9908323, DOI: 10.1523/jneurosci.1526-22.2022.Peer-Reviewed Original ResearchConceptsΑ-syn tg miceΑ-Syn pathologyOlfactory bulb neurogenesisProjection neuronsParkinson's diseaseOlfactory dysfunctionMutant α-synucleinOlfactory deficitsOlfactory pathwaySyn pathologyBehavioral deficitsMouse modelΑ-synucleinOB granule cellsΑ-synuclein pathologyOlfactory systemMonths of ageReduced neurogenesisFunctional deficitsPeriglomerular cellsMotor progressionPathologic changesMultiple symptomsSynaptic terminalsGranule cells
2022
Pharmacological Mechanism of the Non-hallucinogenic 5‑HT2A Agonist Ariadne and Analogs
Cunningham M, Bock H, Serrano I, Bechand B, Vidyadhara D, Bonniwell E, Lankri D, Duggan P, Nazarova A, Cao A, Calkins M, Khirsariya P, Hwu C, Katritch V, Chandra S, McCorvy J, Sames D. Pharmacological Mechanism of the Non-hallucinogenic 5‑HT2A Agonist Ariadne and Analogs. ACS Chemical Neuroscience 2022, 14: 119-135. PMID: 36521179, PMCID: PMC10147382, DOI: 10.1021/acschemneuro.2c00597.Peer-Reviewed Original ResearchConceptsHead-twitch responseParkinson's diseaseHallucinogenic effectsTherapeutic effectTherapeutic potentialClinical therapeutic effectSevere motor deficitsNew drug classesRemarkable therapeutic effectsConsiderable therapeutic potentialComplete remissionRapid remissionMotor deficitsNeurological indicationsTwitch responseClinical resultsReceptor agonistClinical trialsPharmacological mechanismsDrug classesDopamine receptorsMembrane monoamine transporterPreclinical resultsPlasma membrane monoamine transporterGeriatric subjects