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1.
bioRxiv ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39026818

RESUMO

Despite the blockbuster popularity of drugs that act on catecholamine receptors, catecholamine dynamics in human health and disease remain an incomplete picture. Recent advances in fluorescent sensors have enabled unprecedented access to catecholamine dynamics in preclinical animal models, but the requirements of these technologies limit translational value for clinical diagnostics. Here, we present a flexible and convenient tool for fluorescent catecholamine detection by functionalizing optical fibers with single-walled carbon nanotube (SWNT)-based near-infrared catecholamine sensors (nIRCats), a form factor that has potential for more convenient and less invasive clinical translation. We show that these near-infrared functionalized (nIRF) fibers respond to dopamine in a biologically-relevant concentration range (10nM through 1 µM) with a mean ΔF/F0 of 0.022 through 0.411, with no statistically significant effect on signal magnitude after 16-hour exposure to human blood plasma. We further demonstrate the utility of these fibers in as little as 10 µL volumes of clinically relevant biofluids up to 24 weeks after preparation, with a ΔF/F0 of up to 0.059 through 1.127 for 10 nM through 1 µM dopamine. We also introduce a compact, mobile dual-near-infrared fiber photometry rig and demonstrate its success detecting dopamine with 0.005 ΔF/F0 in acute brain slices with nIRF fibers. Together, this fiber-based tool and photometry rig expand the toolbox of catecholamine detection technologies to a broader range of applications.

4.
Semin Cell Dev Biol ; 118: 64-72, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985902

RESUMO

Across species, adolescence is a period of growing independence that is associated with the maturation of cognitive, social, and affective processing. Reorganization of neural circuits within the frontal cortex is believed to contribute to the emergence of adolescent changes in cognition and behavior. While puberty coincides with adolescence, relatively little is known about which aspects of frontal cortex maturation are driven by pubertal development and gonadal hormones. In this review, we highlight existing work that suggests puberty plays a role in the maturation of specific cell types in the medial prefrontal cortex (mPFC) of rodents, and highlight possible routes by which gonadal hormones influence frontal cortical circuit development.


Assuntos
Lobo Frontal/crescimento & desenvolvimento , Puberdade/fisiologia , Adolescente , Animais , Humanos , Camundongos , Ratos
5.
Transl Psychiatry ; 9(1): 230, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530798

RESUMO

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877, P = 6.76E-10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E-8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Ventrículos Laterais/diagnóstico por imagem , Moléculas de Adesão de Célula Nervosa/genética , Transtornos Psicóticos/genética , Adulto , Alelos , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/diagnóstico por imagem , Adulto Jovem
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