Daily alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Socodato, R (Autor) Outra; Henriques, JF (Autor) Outra; Portugal, CC (Autor) Outra; Almeida, TO (Autor) Outra; Tedim Moreira, J (Autor) Outra; Alves, RL (Autor) Outra; Canedo, T (Autor) Outra; Silva, C (Autor) Outra; Magalhaes, A (Autor) Outra; Summavielle, T (Autor) Outra; Relvas, JB (Autor) FMUP

Revista

Título: Science Signaling

Vol. 13

ISSN: 1945-0877

Editora: American Association for the Advancement of Science

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00S-RXC

DOI: 10.1126/scisignal.aba5754

Abstract (EN): Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, which resulted in increased anxiety-like behavior. Mechanistically, alcohol intake increased the engulfment capacity of microglia in a manner dependent on the kinase Src, the subsequent activation of the transcription factor NF-kappa B, and the consequent production of the proinflammatory cytokine TNF. Pharmacological blockade of Src activation or of TNF production in microglia, genetic ablation of Tnf, or conditional ablation of microglia attenuated aberrant synaptic pruning, thereby preventing the neuronal and behavioral effects of the alcohol. Our data suggest that aberrant pruning of excitatory synapses by microglia may disrupt synaptic transmission in response to alcohol abuse.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16