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 mutationsApoptotic Factors and Mitochondrial Complexes Assist Determination of Strain-Specific Susceptibility of Mice to Parkinsonian Neurotoxin MPTP.
Yarreiphang H, Vidyadhara DJ, Nambisan AK, Raju TR, Sagar BKC, Alladi PA. Apoptotic Factors and Mitochondrial Complexes Assist Determination of Strain-Specific Susceptibility of Mice to Parkinsonian Neurotoxin MPTP. Mol Neurobiol 2023, 60: 4778-4794. PMID: 37162724, DOI: 10.1007/s12035-023-03372-1.Peer-Reviewed Original ResearchDopamine 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 subjectsSubcellular Fractionation for the Isolation of Synaptic Components from the Murine Brain.
Massaro Tieze S, Chandra SS, Vidyadhara DJ. Subcellular Fractionation for the Isolation of Synaptic Components from the Murine Brain. Journal Of Visualized Experiments 2022 PMID: 36190269, PMCID: PMC10936730, DOI: 10.3791/64574.Peer-Reviewed Original ResearchConceptsSubcellular fractionationPost-synaptic compartmentsBiochemical isolationSub-synaptic compartmentsSynaptic cytosolPlasma membraneMolecular basisEnrichment analysisNeuronal preMolecular etiologySynaptic vesiclesSynaptic terminalsSynaptic plasma membranesSynaptic componentsBrain tissue homogenizationSynaptic terminal structureTerminal structureActive stateNeuronal communicationMurine brainSynaptic structureFunctional characteristicsMouse brainHypotonic lysisSynaptic dysfunctionNeuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy
Boddupalli CS, Nair S, Belinsky G, Gans J, Teeple E, Nguyen TH, Mehta S, Guo L, Kramer ML, Ruan J, Wang H, Davison M, Kumar D, Vidyadhara D, Zhang B, Klinger K, Mistry PK. Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy. ELife 2022, 11: e79830. PMID: 35972072, PMCID: PMC9381039, DOI: 10.7554/elife.79830.Peer-Reviewed Original ResearchConceptsNeuronopathic Gaucher diseaseAmelioration of neuroinflammationNK cellsGaucher diseaseSerum neurofilament light chainInvolvement of microgliaActivation of microgliaRole of microgliaProminent pathological featureNeurofilament light chainBlood-derived macrophagesRare neurodegenerative disorderGlucosylceramide synthaseNeuroinflammation pathwaysSerum NFMicroglia activationNeuronal injuryImmune infiltratesImproved survivalBrain macrophagesPathological featuresGD patientsClinical trialsMacrophage compartmentPatient management
2021
Differences in Neuronal Numbers, Morphology, and Developmental Apoptosis in Mice Nigra Provide Experimental Evidence of Ontogenic Origin of Vulnerability to Parkinson's Disease.
Vidyadhara DJ, Yarreiphang H, Raju TR, Alladi PA. Differences in Neuronal Numbers, Morphology, and Developmental Apoptosis in Mice Nigra Provide Experimental Evidence of Ontogenic Origin of Vulnerability to Parkinson's Disease. Neurotoxicity Research 2021, 39: 1892-1907. PMID: 34762290, DOI: 10.1007/s12640-021-00439-6.Peer-Reviewed Original Research
2019
Small molecule modulator of aggrephagy regulates neuroinflammation to curb pathogenesis of neurodegeneration.
Sn S, Pandurangi J, Murumalla R, Dj V, Garimella L, Acharya A, Rai S, Paul A, Yarreiphang H, Pillai MS, Giridharan M, Clement JP, Alladi PA, Saiyed T, Manjithaya R. Small molecule modulator of aggrephagy regulates neuroinflammation to curb pathogenesis of neurodegeneration. EBioMedicine 2019, 50: 260-273. PMID: 31727601, PMCID: PMC6921191, DOI: 10.1016/j.ebiom.2019.10.036.Peer-Reviewed Original ResearchRole of the endolysosomal system in Parkinson’s disease
Vidyadhara DJ, Lee JE, Chandra SS. Role of the endolysosomal system in Parkinson’s disease. Journal Of Neurochemistry 2019, 150: 487-506. PMID: 31287913, PMCID: PMC6707858, DOI: 10.1111/jnc.14820.Peer-Reviewed Original ResearchConceptsHealthy mitochondrial poolParkinson's diseaseRME-8Synaptic endocytosisEndolysosomal sortingEndolysosomal systemDysfunctional mitochondriaPD geneticsMitochondrial poolKey proteinsEarly pathomechanismLysosomal functionSystem genesCell deathKey pathwaysCommon risk factorsCommon neurodegenerative disorderL pathwayMutationsPD pathogenesisL-systemsImportant pathwayAutophagyDopaminergic neuronsPathwayAdmixing MPTP-resistant and MPTP-vulnerable mice enhances striatal field potentials and calbindin-D28K expression to avert motor behaviour deficits.
Vidyadhara DJ, Sasidharan A, Kutty BM, Raju TR, Alladi PA. Admixing MPTP-resistant and MPTP-vulnerable mice enhances striatal field potentials and calbindin-D28K expression to avert motor behaviour deficits. Behavioural Brain Research 2019, 360: 216-227. PMID: 30529402, DOI: 10.1016/j.bbr.2018.12.015.Peer-Reviewed Original Research
2018
Pluchea lanceolata protects hippocampal neurons from endothelin-1 induced ischemic injury to ameliorate cognitive deficits.
Mundugaru R, Sivanesan S, Popa-Wagner A, Udaykumar P, Kirubagaran R, Kp G, Vidyadhara DJ. Pluchea lanceolata protects hippocampal neurons from endothelin-1 induced ischemic injury to ameliorate cognitive deficits. Journal Of Chemical Neuroanatomy 2018, 94: 75-85. PMID: 30273663, DOI: 10.1016/j.jchemneu.2018.09.002.Peer-Reviewed Original ResearchModulation of Autophagy by a Small Molecule Inverse Agonist of ERRα Is Neuroprotective.
Suresh SN, Chavalmane AK, Pillai M, Ammanathan V, Vidyadhara DJ, Yarreiphang H, Rai S, Paul A, Clement JP, Alladi PA, Manjithaya R. Modulation of Autophagy by a Small Molecule Inverse Agonist of ERRα Is Neuroprotective. Frontiers In Molecular Neuroscience 2018, 11: 109. PMID: 29686608, PMCID: PMC5900053, DOI: 10.3389/fnmol.2018.00109.Peer-Reviewed Original Research
2017
Admixing of MPTP-Resistant and Susceptible Mice Strains Augments Nigrostriatal Neuronal Correlates to Resist MPTP-Induced Neurodegeneration.
Vidyadhara DJ, Yarreiphang H, Raju TR, Alladi PA. Admixing of MPTP-Resistant and Susceptible Mice Strains Augments Nigrostriatal Neuronal Correlates to Resist MPTP-Induced Neurodegeneration. Molecular Neurobiology 2017, 54: 6148-6162. PMID: 27704331, DOI: 10.1007/s12035-016-0158-y.Peer-Reviewed Original ResearchA novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity.
Suresh SN, Chavalmane AK, Dj V, Yarreiphang H, Rai S, Paul A, Clement JP, Alladi PA, Manjithaya R. A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity. Autophagy 2017, 13: 1221-1234. PMID: 28350199, PMCID: PMC5529071, DOI: 10.1080/15548627.2017.1302045.Peer-Reviewed Original Research
2016
Differential expression of calbindin in nigral dopaminergic neurons in two mice strains with differential susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Vidyadhara DJ, Yarreiphang H, Abhilash PL, Raju TR, Alladi PA. Differential expression of calbindin in nigral dopaminergic neurons in two mice strains with differential susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Journal Of Chemical Neuroanatomy 2016, 76: 82-89. PMID: 26775762, DOI: 10.1016/j.jchemneu.2016.01.001.Peer-Reviewed Original Research
2015
Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta.
Jyothi HJ, Vidyadhara DJ, Mahadevan A, Philip M, Parmar SK, Manohari SG, Shankar SK, Raju TR, Alladi PA. Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta. Neurobiology Of Aging 2015, 36: 3321-3333. PMID: 26433682, DOI: 10.1016/j.neurobiolaging.2015.08.024.Peer-Reviewed Original Research