RESUMO
Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A). Calibration to absolute density values (pmol/ml) was achieved by leveraging postmortem human brain autoradiography data. The atlas unveils distinctive cortical and subcortical gradients of synapse density that reflect functional topography and hierarchical order from core sensory to higher-order integrative areas-a distribution that diverges from SV2A mRNA patterns. Furthermore, we found a positive association between IQ and SV2A density in several higher-order cortical areas. This new resource will help advance our understanding of brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future neuroscience research.
Assuntos
Encéfalo , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso , Tomografia por Emissão de Pósitrons , Sinapses , Humanos , Sinapses/metabolismo , Sinapses/fisiologia , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiologia , Adulto , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Tomografia por Emissão de Pósitrons/métodos , Pessoa de Meia-Idade , Atlas como Assunto , Adulto Jovem , Autorradiografia/métodos , IdosoRESUMO
BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking. OBJECTIVE: To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients. METHODS: We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities. RESULTS: In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists. CONCLUSION: In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.