%0 Journal Article
%A Silva Peña, Daniel
%A Martín Velasco, Ana Isabel
%A Villanúa Bernués, María Ángeles
%A Rubio Valladolid, Gabriel
%A Rodríguez De Fonseca, Fernando Antonio
%A Suárez Pérez, Juan
%T Alcohol-induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats
%D 2019
%@ 1355-6215
%U https://hdl.handle.net/20.500.14352/91312
%X Chronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticityand connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cogni-tive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitiveimpairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulat-ing levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent sub-jects with alcohol use disorders (AUDs,N= 58, average of 17.9 years of problematic use and 4.3 months of abstinence)compared with healthy control subjects (N= 22). This association was also explored in a pre-clinical model of adoles-cent rats chronically exposed to alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5–10–20 per-cent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairmentassociated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentrationshowed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasmalevels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampalBdnfmRNA levels andrecognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neu-rotrophic (BdnfandNtf-3) and neurogenic (Mki67,Sox2,Dcx,Ncam1andCalb1) factors, associated to a deactivation ofthe neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a rel-evant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and sug-gest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.
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