Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence

Acta Neuropathologica Communications

Research

Úrsula Pérez-Ramírez¹  David Moratal¹  Patrick Bach²  Falk Kiefer²  Patrick Halli³  Peter Kirsch³  Simone Pfarr⁴  Wolfgang H. Sommer⁵  Alejandro Trouvé-Carpena⁶  Laura Pérez-Cervera⁶  Mohamed Kotb Selim⁶  Silvia De Santis⁶  Santiago Canals⁶  Encarni Marcos⁶  Zahra Ghorbanzad-Ghaziany⁷ 

[1]Center for Biomaterials and Tissue Engineering, Universitat Politècnica de València, Valencia, Spain

[2]Department of Addiction Medicine, Department of Clinical Psychology, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

[3]Department of Psychology, University of Heidelberg, Heidelberg, Germany

[4]Institute of Psychopharmacology, Central Institute of Mental Health, Medical faculty Mannheim, University of Heidelberg, Mannheim, Germany

[5]Institute of Psychopharmacology, Central Institute of Mental Health, Medical faculty Mannheim, University of Heidelberg, Mannheim, Germany

[6]Department of Addiction Medicine, Department of Clinical Psychology, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

[7]Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Sant Joan d’Alacant, Alicante, Spain

[8]Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Sant Joan d’Alacant, Alicante, Spain

[9]Radiation Science and Biomedical Imaging, University of Sherbrooke, Sherbrooke, Québec, Canada

关键词: Fimbria;    Fornix;    DTI;    Diffusion;    White matter;    AUD;    Alcohol;    Prefrontal cortex;    Hippocampus;    Memory;    Flexibility;    Cognitive test;    TMT;   

DOI  :  10.1186/s40478-023-01597-8

 received in 2023-05-09, accepted in 2023-05-30,  发布年份 2023

来源: Springer

【 摘 要 】

IntroductionAlcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology.SummaryFimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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