Neural Circuits & Behavior Process Report // Laia Morato - Stress-induced alterations of eNAMPT impair NAD+/SIRT1 pathway in the nucleus accumbens and reduce sociability
Event details
| Date | 07.03.2019 |
| Hour | 09:30 › 10:30 |
| Speaker | Laia Morato , Prof. Sandi's lab |
| Location | |
| Category | Conferences - Seminars |
Early-life exposure to stressful experiences has been described as a predisposing factor to develop alterations both in metabolism and behavior. Here, we show that exposure to a paradigm of unpredictable stress during the peripubertal period reduces sociability in mice together with alterations in peripheral metabolism, such as increased percentage of fat mass. Remarkably, the protein levels of NAMPT in the adipose tissue of stressed mice are decreased and the blood levels of the cytokine eNAMPT -the extracellular form of the enzyme- predict the behavioral deficits displayed later in life. Aiming at understanding whereby eNAMPT differences can cause alterations in the brain, we analyzed NAD+ levels, expression of mitochondrial genes and neuronal excitability in the nucleus accumbens (NAc), a key brain region for the stress response. We observed that the NAc of stressed mice exhibits an impairment in the NAD+/SIRT1 pathway together with reduced neuronal excitability. Systemic treatment with the NAD+ booster nicotinamide mononucleotide (NMN) or adipose-specific overexpression of Nampt prevents sociability and neuronal excitability deficits in the NAc. Moreover, genetic and pharmacological modulation of SIRT1 expression in the NAc rescues sociability deficits. These findings strengthen the idea of eNAMPT as a mediator of fat-brain communication and pave the way for the use of NAD+ boosters to treat stress-related disorders such as depression.
Practical information
- Informed public
- Free
Organizer
- Brain Mind Intitute