Cross-Frequency Phase-Amplitude Coupling between Hippocampal Theta and Gamma Oscillations during Recall Destabilizes Memory and Renders It Susceptible to Reconsolidation Disruption.

Avoidance memory reactivation at recall triggers theta-gamma hippocampal phase amplitude coupling (hPAC) only when it elicits hippocampus-dependent reconsolidation. However, it is not known whether there is a causal relationship between these phenomena. We found that in adult male Wistar rats, silencing the medial septum during recall did not affect avoidance memory expression or maintenance but abolished hPAC and the amnesia caused by the intrahippocampal administration of reconsolidation blockers, both of which were restored by concomitant theta burst stimulation of the fimbria-fornix pathway. Remarkably, artificial hPAC generated by fimbria-fornix stimulation during recall of a learned avoidance response naturally resistant to hippocampus-dependent reconsolidation made it susceptible to reactivation-dependent amnesia. Our results indicate that hPAC mediates the destabilization required for avoidance memory reconsolidation and suggest that the generation of artificial hPAC at recall overcomes the boundary conditions of this process.SIGNIFICANCE STATEMENT Theta-gamma hippocampal phase-amplitude coupling (hPAC) increases during the induction of hippocampus-dependent avoidance memory reconsolidation. However, whether hPAC plays a causal role in this process remains unknown. Using behavioral, electrophysiological, optogenetic, and biochemical tools in adult male Wistar rats, we demonstrate that reactivation-induced hPAC is necessary for avoidance memory destabilization, and that artificial induction of this patterned activity during recall of reconsolidation-resistant aversive memories renders them liable to the amnesic effect of reconsolidation inhibitors.

Changes in trophoblasts gene expression in response to perchlorate exposition.

Contaminated water with chlorates is a public health problem associated with iodine deficiency. Epidemiological evidence shows that iodine deficiency is a risk factor for preeclampsia (PE). In this study we use human BeWo trophoblast cells exposed to perchlorate (KClO4) and changes in gene expression were analyzed by microarrays, quantitative RT-PCR (qRT-PCR) and immunoblot. The microarray analysis identified 48 transcripts up-regulated and 112 down-regulated in comparison with non-exposed trophoblast. The qRT-PCR analysis confirmed changes in GAS7, PKP2, Emilin, Dynatic 3, protocadherins 11, 15, gamma A12, EGFR, SAFB1, ACE2, ANXA2, Apoliprotein E, SREBF1, and C/EBP-ß. KClO4 exposition decreased the mRNA and protein of C/EBP-ß and GPX4. Also, we observed a nuclear translocation of HIF1α protein, and increase in both Snail and ACE2 protein by immunoblot. These effects were accompanied by an increases in ROS and nitric oxide. In conclusion, our results show that exposure to KClO4 alters genes involved in migration, adhesion, differentiation, and correlate with the increase of oxidative stress and nitric oxide production in trophoblast cells. It is possible that iodine deficiency is associated with these processes. However, further studies are required to corroborate the role of iodine in trophoblast cells.

The CCAAT box in the proximal SERCA2 gene promoter regulates basal and stress-induced transcription in cardiomyocytes.

The cardiac sarco/endoplasmic reticulum Ca2+-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated. In this work, we show that in cellular cultures of neonatal rat ventricular myocytes, the treatment with Tg or the calcium ionophore A23187 increases the SERCA2a mRNA and protein abundance, as well as the transcriptional activity of two chimeric human SERCA2 gene constructs, containing -254 and -2579 bp of 5'-regulatory region cloned in the pGL3-basic vector and transiently transfected in cultured cardiomyocytes. We found that the ERSE present in the SERCA2 proximal promoter contains a CCAAT box that is involved in basal and ERS-mediated hSERCA2 transcriptional activation. The EMSA results showed that the CCAAT box present in the ERSE recruits the NF-Y transcription factor. Additionally, by ChIP assays, we confirmed in vivo binding of NF-Y and C/EBPß transcription factors to the SERCA2 gene proximal promoter.

Choline kinase alpha expression during RA-induced neuronal differentiation: role of C/EBPß.

Neuronal differentiation is a complex process characterized by a halt in proliferation and extension of neurites from the cell body. This process is accompanied by changes in gene expression that mediate the redirection leading to neurite formation and function. Acceleration of membrane phospholipids synthesis is associated with neurite elongation, and phosphatidylcholine (PtdCho) is the major membrane phospholipid in mammalian cells. The transcription of two genes in particular encoding key enzymes in the CDP-choline pathway for PtdCho biosynthesis are stimulated; the Chka gene for choline kinase (CK) alpha isoform and the Pcyt1a gene for the CTP:phosphocholine cytidylyltransferase (CCT) alpha isoform. We report that the stimulation of CKα expression during retinoic acid (RA) induced differentiation depends on a promoter region that contains two CCAAT/Enhancer-binding Protein-ß (C/EBPß) sites. We demonstrate that during neuronal differentiation of Neuro-2a cells, RA induces Chka expression by a mechanism that involves ERK1/2 activation which triggers C/EBPß expression. Elevated levels of C/EBPß bind to the Chka proximal promoter (Box1) inducing CKα expression. In addition we identified a downstream sequence named Box2 which together with Box1 is required for the promoter to reach the full induction. This is the first elucidation of the mechanism by which the expression of Chka is coordinately regulated during neuronal differentiation.