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1.
Stem Cell Reports ; 18(7): 1482-1499, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37352848

RESUMO

The adult subventricular zone (SVZ) is a neurogenic niche that continuously produces newborn neurons. Here we show that serine racemase (SR), an enzyme that catalyzes the racemization of L-serine to D-serine and vice versa, affects neurogenesis in the adult SVZ by controlling de novo fatty acid synthesis. Germline and conditional deletion of SR (nestin precursor cells) leads to diminished neurogenesis in the SVZ. Nestin-cre+ mice showed reduced expression of fatty acid synthase and its substrate malonyl-CoA, which are involved in de novo fatty acid synthesis. Global lipidomic analyses revealed significant alterations in different lipid subclasses in nestin-cre+ mice. Decrease in fatty acid synthesis was mediated by phospho Acetyl-CoA Carboxylase that was AMP-activated protein kinase independent. Both L- and D-serine supplementation rescued defects in SVZ neurogenesis, proliferation, and levels of malonyl-CoA in vitro. Our work shows that SR affects adult neurogenesis in the SVZ via lipid metabolism.


Assuntos
Ventrículos Laterais , Neurogênese , Camundongos , Animais , Ventrículos Laterais/metabolismo , Nestina/metabolismo , Neurogênese/fisiologia , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos
2.
Virol J ; 11: 161, 2014 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-25186971

RESUMO

BACKGROUND: Borna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells of humans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability. METHOD: This first report from the Middle East aimed to determine BDV infection prevalence in Iranian acute psychiatric disorder patients and healthy controls through circulating immune complexes (CIC), antibodies (Ab) and antigen (pAg) in blood plasma using a standardized triple enzyme immune assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood donors, and 131 healthy controls) were assayed and data analyzed quantitatively and qualitatively. RESULTS: CICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5% controls; 33.3% blood donors). In psychiatric patients CIC prevalence was higher than in controls (40.4%) and significantly correlating with bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR = 1.65). CIC values were significantly elevated in bipolar (p = 0.001) and major depressive disorder (p = 0.029) patients as compared to controls, and in females compared to males (p = 0.031). CONCLUSION: This study supports a similarly high prevalence of subclinical human BDV infections in Iran as reported for central Europe, and provides again an indication for the correlation of BDV infection and mood disorders. Further studies should address the morbidity risk for healthy carriers and those with elevated CIC levels, along with gender disparities.


Assuntos
Transtorno Bipolar/complicações , Doença de Borna/diagnóstico , Vírus da Doença de Borna/isolamento & purificação , Transtorno Depressivo Maior/complicações , Adolescente , Adulto , Idoso , Transtorno Bipolar/epidemiologia , Doadores de Sangue , Doença de Borna/epidemiologia , Doença de Borna/virologia , Estudos de Casos e Controles , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
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