Loss of leptin-induced modulation of hippocampal synaptic trasmission and signal transduction in high-fat diet-fed mice

Salvatore Fusco, Marcello D'Ascenzo, Claudio Grassi, Marco Mainardi, Matteo Spinelli, Federico Scala, Andrea Mattera

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

18 Citazioni (Scopus)

Abstract

Hippocampal plasticity is triggered by a variety of stimuli including sensory inputs, neurotrophins and inflammation. Leptin, whose primary function is to regulate food intake and energy expenditure, has been recently shown to affect hippocampal neurogenesis and plasticity. Interestingly, mice fed a high-fat diet (HFD) exhibit impaired hippocampal function, but the underlying mechanisms are poorly understood. To address this issue, we compared leptin responsiveness of hippocampal neurons in control and HFD-fed mice by combining single-cell electrophysiology and biochemical assays. We found that leptin modulated spontaneous and evoked synaptic transmission in control, but not HFD, mice. This functional impairment was paralleled by blunted activation of STAT-3, one of the key signal transduction pathways controlled by the fully functional isoform of the leptin receptor, ObRb. In addition, SOCS-3 expression was non-responsive to leptin, indicating that modulation of negative feedback impinging on ObRb was also altered. Our results advance the understanding of leptin action on hippocampal plasticity and, more importantly, suggest that leptin resistance is a key determinant of hippocampal dysfunction associated with hypercaloric diet.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine11
RivistaFrontiers in Cellular Neuroscience
Volume2017
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • CA1
  • Cellular and Molecular Neuroscience
  • ObR
  • Patch-clamp
  • SOCS-3
  • STAT-3
  • Schaffer collateral

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