4.7 Article

Vascular Endothelial Growth Factor as a Potential Biomarker of Neuroinflammation and Frontal Cognitive Impairment in Patients with Alcohol Use Disorder

Journal

BIOMEDICINES
Volume 10, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10050947

Keywords

alcohol use disorders; addiction; VEGFA; blood-brain barrier; chemokines; fractalkine; neuroinflammation; cognitive dysfunction; neurodegeneration; dementia

Funding

  1. RETICS Red de Trastornos Adictivos
  2. Instituto de Salud Carlos III (ISCIII)
  3. Ministerio de Ciencia e Innovacion
  4. European Regional Development Funds-European Union (ERDF-EU) [RD16/0017/0001, RD16/0017/003]
  5. ISCIII, ERDF-EU [PI20/01399, PI19/01577, PI19/00886]
  6. Ministerio de Sanidad, Delegacion de Gobierno para el Plan Nacional sobre Drogas [PND 2020I048, PND 2019I040, PND 2018I044, PND 2018I033, PND 2016I024, PND 2018I037]
  7. Consejeria de Salud y Familia, Junta de Andalucia (Neuro-RECA) [RIC-0111-2019, CPII19/00022, CPII19/00031]
  8. Servicio Andaluz de Salud, Consejeria de Salud y Familia, Junta de Andalucia [C1-0049-2019]
  9. Ministry of Economy and Knowledge-Regional Government of Andalucia [UMA-FEDERJA-076]
  10. ERDF-EU
  11. ISCIII ERDF/ESF [FI18/00249]
  12. ISCIII [CD19/00019]

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This study suggests that alcohol-induced alterations in chemokines and VEGFA might contribute to the neuroinflammation and cognitive impairment associated with Alcohol Use Disorder (AUD). Monitoring VEGFA/chemokine levels could be used as potential biomarkers for cognitive impairment in AUD patients.
(1) Background: Alcohol Use Disorder (AUD) is associated with functional disruption of several brain structures that may trigger cognitive dysfunction. One of the mechanisms of alcohol-associated cognitive impairment has been proposed to arise from its direct impact on the immune system, which culminates in the release of cytokines and chemokines which can eventually reach the brain. Alcohol can also disrupt the blood-brain barrier, facilitating the penetration of pro-inflammatory molecules throughout vascular endothelial growth factor A (VEGFA). Thus, alcohol-induced alterations in chemokines and VEGFA might contribute to the neuroinflammation and cognitive impairment associated with AUD. (2) Methods: The present cross-sectional study investigates whether patients with AUD (n = 86) present cognitive disability associated to alterations in plasma concentration of SDF-1, fractalkine, eotaxin, MCP-1, MIP-1 alpha and VEGFA when compared to control subjects (n = 51). (3) Results: The analysis indicated that SDF-1 and MCP-1 concentrations were higher in AUD patients than in controls. Concentrations of VEGFA were higher in AUD patients with severe frontal deficits, and the score of frontal lobe functions was negatively correlated with VEGFA and fractalkine. Acute alcohol effects on VEGFA plasma levels in healthy volunteers demonstrated the induction of VEGFA release by heavy alcohol drinking. VEGFA was positively correlated with pro-inflammatory chemokines in AUD patients with frontal cognitive impairment. (4) Conclusions: we propose VEGFA/chemokine monitoring as biomarkers of potential cognitive impairment in AUD patients.

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