2024
Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome
Xu J, Frankovich J, Liu R, Thienemann M, Silverman M, Farhadian B, Willett T, Manko C, Columbo L, Leibold C, Vaccarino F, Che A, Pittenger C. Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome. Brain Behavior And Immunity 2024, 122: 241-255. PMID: 39084540, DOI: 10.1016/j.bbi.2024.07.044.Peer-Reviewed Original ResearchPediatric Autoimmune Neuropsychiatric Disorders Associated with StreptococcusPediatric acute-onset neuropsychiatric syndromeStriatal cholinergic interneuronsCholinergic interneuronsObsessive-compulsive symptomsModulate basal ganglia functionNeuropsychiatric syndromeSignificant obsessive-compulsive symptomsBasal ganglia functionEx vivo brain slicesSevere food restrictionElevated antibodiesClinical historyPatient plasmaNeuropsychiatric manifestationsStreptococcus infectionBrain slicesSymptom flaresControl plasmaFood restrictionSerum antibodiesHuman brainInfectionAbrupt onsetClinical contextActivation of M4 muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome
Cadeddu R, Braccagni G, Branca C, van Luik E, Pittenger C, Thomsen M, Bortolato M. Activation of M4 muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome. British Journal Of Pharmacology 2024, 181: 3064-3081. PMID: 38689378, DOI: 10.1111/bph.16392.Peer-Reviewed Original ResearchPositive allosteric modulatorsD1CT-7 miceTourette syndromeMouse model of TSStriatal cholinergic interneuronsTic-like behavioursC-Fos levelsModel of TSActivate c-fosM4 muscarinic receptorsMuscarinic receptorsStriatal acetylcholineMouse modelStriatal expressionTic-likeStriatal levelsCholinergic interneuronsVU0467154Current pharmacotherapyXanomelineReceptor agonistsAllosteric modulatorsC-fosReceptor antagonistStriatum
2023
Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology
Cadeddu R, Van Zandt M, Santovito L, Odeh K, Anderson C, Flanagan D, Nordkild P, Pinna G, Pittenger C, Bortolato M. Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology. Neuropsychopharmacology 2023, 48: 1288-1299. PMID: 37198434, PMCID: PMC10354086, DOI: 10.1038/s41386-023-01603-6.Peer-Reviewed Original ResearchConceptsEffects of allopregnanoloneTourette syndromeCholinergic interneuronsAcute stressPrefrontal cortexPrepulse inhibitionTic pathophysiologyMouse modelAdverse effectsStriatal cholinergic interneuronsDeficient prepulse inhibitionSeverity of ticsPost-mortem studiesPharmacological antagonismPPI deficitsNeurosteroid allopregnanoloneMale miceAdministration doseAllopregnanoloneAnimal modelsBehavioral pathologySymptom severityAcute stressorYoung adulthoodAP levels
2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types