Browsing by Author "Francisco Codocedo, Juan"

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    ATP Induces NO Production in Hippocampal Neurons by P2X7 Receptor Activation Independent of Glutamate Signaling
    (2013) Francisco Codocedo, Juan; Alejandro Godoy, Juan; Ines Poblete, Maria; Inestrosa, Nibaldo C.; Pablo Huidobro-Toro, Juan
    To assess the putative role of adenosine triphosphate (ATP) upon nitric oxide (NO) production in the hippocampus, we used as a model both rat hippocampal slices and isolated hippocampal neurons in culture, lacking glial cells. In hippocampal slices, additions of exogenous ATP or 2'(3')-O-(4-Benzoylbenzoyl) ATP (Bz-ATP) elicited concentration-dependent NO production, which increased linearly within the first 15 min and plateaued thereafter; agonist EC50 values were 50 and 15 mu M, respectively. The NO increase evoked by ATP was antagonized in a concentration-dependent manner by Coomassie brilliant blue G (BBG) or by N-omega-propyl-L-arginine, suggesting the involvement of P2X(7)Rs and neuronal NOS, respectively. The ATP induced NO production was independent of N-methyl-D-aspartic acid (NMDA) receptor activity as effects were not alleviated by DL-2-Amino-5-phosphonopentanoic acid (APV), but antagonized by BBG. In sum, exogenous ATP elicited NO production in hippocampal neurons independently of NMDA receptor activity.
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    Effects of long-lasting social isolation and re-socialization on cognitive performance and brain activity: a longitudinal study in Octodon degus
    (2020) Rivera, Daniela S.; Lindsay, Carolina B.; Oliva, Carolina A.; Francisco Codocedo, Juan; Bozinovic, Francisco; Inestrosa, Nibaldo C.
    Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function. Here, we investigated the effects of long-term social isolation on working memory, spatial learning/memory, hippocampal synaptic transmission, and synaptic proteins in the brain of adult female and male Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects, makes it a unique animal model that can be highly applicable for further social, emotional, cognitive, and aging studies. These animals were socially isolated from post-natal and post-weaning until adulthood. We also evaluated if re-socialization would be able to compensate for reactive stress responses in chronically stressed animals. We showed that long-term social isolation impaired the HPA axis negative feedback loop, which can be related to cognitive deficits observed in chronically stressed animals. Notably, re-socialization restored it. In addition, we measured physiological aspects of synaptic transmission, where chronically stressed males showed more efficient transmission but deficient plasticity, as the reverse was true on females. Finally, we analysed synaptic and canonical Wnt signalling proteins in the hypothalamus, hippocampus, and prefrontal cortex, finding both sex-and brain structure-dependent modulation, including transient and permanent changes dependent on stress treatment.
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    Neurosteroids differentially modulate P2X4 ATP-gated channels through non-genomic interactions
    (2009) Francisco Codocedo, Juan; Rodriguez, Felipe E.; Pablo Huidobro-Toro, Juan
    As neuroactive steroids modulate several ionotropic receptors, we assessed whether the ATP-gated currents elicited by P2X(4) receptors are modulated by these compounds. We transfected HEK293 cells or injected Xenopus laevis oocytes with the cDNA coding for rat P2X(4) receptor. Application of 0.1-10 mu M alfaxolone potentiated within 60-s the 1 mu M ATP-evoked currents with a maximal potentiation of 1.8 and 2.6-fold in HEK293 or oocytes cells respectively. Allopregnalolone or 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC) also potentiated the ATP-gated currents but with a maximal effect only averaging 1.25 and 1.35-fold respectively. In contrast, 0.3-10 mu M pregnanolone, but not its sulfated derivative, inhibited the ATP-gated currents; the maximal inhibition reached 40% in both cell types. THDOC, but not other neurosteroids increased significantly the tau(off) of the ATP-evoked currents, revealing another mode of neurosteroid modulation. Sexual steroids such as 17 beta-estradiol or progesterone were inactive revealing explicit structural requirements. Alfaxolone or THDOC at concentrations 30- to 100-fold larger than required to modulate the receptor, gated the P2X(4) receptor eliciting ATP-like currents that were reduced with suramin or brilliant blue G, but potentiated the P2X(4) receptor more than 10-fold by 10 mu M zinc. In conclusion, neurosteroids rapidly modulate via non-genomic mechanisms and with nanomolar potencies, the P2X4 receptor interacting likely at distinct modulator sites.