Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior

Instituto Cajal, CSIC, Madrid, Spain.
PLoS ONE (Impact Factor: 3.23). 08/2012; 7(8):e42911. DOI: 10.1371/journal.pone.0042911
Source: PubMed


Mitochondrial uncoupling protein 2 (UCP2) is induced by cellular stress and is involved in regulation of fuel utilization, mitochondrial bioenergetics, cell proliferation, neuroprotection and synaptogenesis in the adult brain. Here we show that natural birth in mice triggers UCP2 expression in hippocampal neurons. Chemical inhibition or genetic ablation of UCP2 lead to diminished neuronal number and size, dendritic growth and synaptogenezis in vitro and impaired complex behaviors in the adult. These data reveal a critical role for Ucp2 expression in the development of hippocampal neurons and circuits and hippocampus-related adult behaviors.


Available from: Marcelo O Dietrich
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    • "Their sequences were 5 -CTT GCA AGA CAG AGA GCC G-3 (forward) and 5 -CTG GGT GTC TGA TTG CTG TTC-3 (reverse), which resulted in a 210-bp PCR product. The sequences of the primers amplifying the murine TFAM cDNA were 5 -GGA ATG TGG AGC GTG CTA AAA-3 (forward) and 5 -TGC TGG AA A AAC ACT TCG GAA TA-3 (reverse); these were chosen from a publication [17] "
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    ABSTRACT: The cytotoxicity of quercetin is not well understood. Using an ICR murine model, we unexpectedly found that mice exposed to 7 Gy total body irradiation (TBI) exhibited general in vivo toxicity after receiving quercetin (100 mg/kg PO), whereas this result was not observed in mice that received TBI only. In order to understand the involvement of alterations in mitochondrial biogenesis, we used a real-time qPCR to analyze the mitochondrial DNA copy number (mtDNAcn) by amplifying the MTRNR1 (12S rRNA) gene in murine bone marrow. We also utilized reverse transcription qPCR to determine the mRNA amounts transcribed from the polymerase gamma (POLG), POLG2, and mammalian mitochondrial transcription factor A (TFAM) genes in the tissue. In the mice exposed to TBI combined with quercetin, we found: (1) the radiation-induced increase of mtDNAcn was inhibited with a concurrent significant decrease in POLG expression; (2) TFAM expression was significantly increased; and (3) the expression of POLG2 was not influenced by the treatments. These data suggest that the overall toxicity was in part associated with the decrease in mtDNAcn, an effect apparently caused by the inhibition of POLG expression and overexpression of TFAM; unaltered POLG2 expression did not seem to contribute to toxicity.
    Toxicology Reports 12/2014; 1. DOI:10.1016/j.toxrep.2014.07.014
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    • "These data support the findings of some other research groups that have described the presence of UCP2 at the protein level in immune and pluripotent stem cells [13], [18]–[20] as well as in cancer cells [21]–[23]. However, the investigation of UCP2 functions in the brain continues to be an issue of scientific discussion [24]–[27]. "
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    PLoS ONE 02/2014; 9(2):e88474. DOI:10.1371/journal.pone.0088474 · 3.23 Impact Factor
    • "Should we examine further variations in stress responsiveness based on delivery method? Also, the altered response to maternal separation could indicate an alteration in stress response that could be related to later attention or spatial memory disorders similar to those found in rats, as described by Simon-Areces [18]. "
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