Dopamine neuron-derived IGF-1 controls dopamine neuron firing, skill learning, and exploration

Pristerà, Alessandro; Blomeley, Craig; Lopes, Emanuel F.; Threlfell, Sarah; Merlini, Elisa; Burdakov, Denis; Cragg, Stephanie J.; Guillemot, François; Ang, Siew‐Lan

doi:10.1073/pnas.1806820116

Cited by 55 publications

(42 citation statements)

References 74 publications

(105 reference statements)

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“…In the mammalian central nervous system, DA controls many processes [262,264], such as feeding and locomotion [265]; it is also involved in the mechanisms of cognition and ‘adaptive’ memory formation, influencing the hippocampal long term potentiation (LTP) [266], and upregulates BDNF in the prefrontal cortex [267]. DA most probably interacts with other neurotransmitters and neuromodulators and, for example, it has been recently demonstrated that midbrain mice DA neurons also release IGF-1 that modulates DA release and concentration as well as neuronal firing [268].…”

Section: Exercise-dependent Production Of Dopamine Endocannabinoimentioning

confidence: 99%

Physical Activity and Brain Health

Liegro

Schiera

Proia

et al. 2019

Genes

250

164

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Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It has been also acknowledged that lifestyle and diet can induce epigenetic modifications which modify chromatin structure and gene expression, thus causing even heritable metabolic outcomes. Many studies have shown that PA can reverse at least some of the unwanted effects of sedentary lifestyle, and can also contribute in delaying brain aging and degenerative pathologies such as Alzheimer’s Disease, diabetes, and multiple sclerosis. Most importantly, PA improves cognitive processes and memory, has analgesic and antidepressant effects, and even induces a sense of wellbeing, giving strength to the ancient principle of “mens sana in corpore sano” (i.e., a sound mind in a sound body). In this review we will discuss the potential mechanisms underlying the effects of PA on brain health, focusing on hormones, neurotrophins, and neurotransmitters, the release of which is modulated by PA, as well as on the intra- and extra-cellular pathways that regulate the expression of some of the genes involved.

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Section: Exercise-dependent Production Of Dopamine Endocannabinoimentioning

confidence: 99%

Physical Activity and Brain Health

Liegro

Schiera

Proia

et al. 2019

Genes

250

164

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“…IGF1R is known as a transmembrane receptor tyrosine kinase which is implicated in the regulation of IGF bioactivity [13]. Interactions between cells utilizing the IGF-1/IGF1R signalling cascades play a key role in the survival of neuronal cells against stress and injury [12,15].…”

Section: Introductionmentioning

confidence: 99%

LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury

Zhang¹,

Song²,

Feng³

et al. 2019

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The purpose of this study was to evaluate whether FGD5-AS1 participates in oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury and the detailed mechanism. An OGD/R model was established using the primary cortical neuron isolated from the brains of Sprague-Dawley rats. qRT-PCR and western blot were performed to detect the RNA and protein expression levels, respectively. Cell counting kit 8 (CCK8) and flow cytometry assays were used to evaluate the proliferation and apoptosis of neurons. The luciferase reporter assay was used to verify the interaction between lncRNA FGD5-AS1 and miRNA-223. We found that the expression of FGD5-AS1 is decreased in neurons suffering from OGD/R. Up-regulation of FGD5-AS1 could recover proliferation and inhibit apoptosis of OGD/R-injured neurons. In addition, the interaction between FGD5-AS1 and miRNA-223 were verified. The expression of miRNA-223 was negatively correlated with the level of FGD5-AS1. In turn, the expression of insulin-like growth factor-1 receptor (IGFIR, a target gene of miR-223) was positively associated with the level of FGD5-AS1. Simultaneously down-regulating miR-223 and over-expressing FGD5-AS1 as well as IGF1R exhibited an additional effect of extenuating OGD/R damage i.e. increasing neuron proliferation and reducing neuron apoptosis. In conclusion, our findings indicated that FGD5-AS1 may protect the neuron against OGD/R injury via acting as a ceRNA for miR-223 to mediate IGF1R expression, which contributes to a deeper understanding of ischemic stroke and provide a promising therapeutic target for this disease.

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“…DA neurons present IGF‐1 receptors (IGF‐1R), 173,174 and administration of IGF‐1 prevents degeneration of DA neurons in Parkinson's disease (PD) models through the activation of the PI3K/AKT pathway 175,176 . It has recently been discovered that a large population of VTA and SNc DA neurons present endogenous somatic but not axonal release of IGF‐1 in response to depolarization as a feed‐forward mechanism, blocking somatodendritic release of DA and D2 autoreceptor‐mediated inhibition 174 . Particularly, IGF‐1 activates the mTOR pathway, so specific deletion of IGF‐1 in DA neurons decreases phosphorylation of mTOR downstream element S6 174 .…”

Section: Trophic Factors Regulate Da Homeostasis Through Mtor Pathwaymentioning

confidence: 99%

“…It has recently been discovered that a large population of VTA and SNc DA neurons present endogenous somatic but not axonal release of IGF‐1 in response to depolarization as a feed‐forward mechanism, blocking somatodendritic release of DA and D2 autoreceptor‐mediated inhibition 174 . Particularly, IGF‐1 activates the mTOR pathway, so specific deletion of IGF‐1 in DA neurons decreases phosphorylation of mTOR downstream element S6 174 . IGF‐1 lacking DA neurons also present decreased TH activating phosphorylation in Ser40, whose activity is controlled by mTOR as previously described in DA neurons 154,174 .…”

Section: Trophic Factors Regulate Da Homeostasis Through Mtor Pathwaymentioning

confidence: 99%

Energy sensors in drug addiction: A potential therapeutic target

2020

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Addiction is defined as the repeated exposure and compulsive seek of psychotropic drugs that, despite the harmful effects, generate relapse after the abstinence period. The psychophysiological processes associated with drug addiction (acquisition/expression, withdrawal, and relapse) imply important alterations in neurotransmission and changes in presynaptic and postsynaptic plasticity and cellular structure (neuroadaptations) in neurons of the reward circuits (dopaminergic neuronal activity) and other corticolimbic regions. These neuroadaptation mechanisms imply important changes in neuronal energy balance and protein synthesis machinery. Scientific literature links drug‐induced stimulation of dopaminergic and glutamatergic pathways along with presence of neurotrophic factors with alterations in synaptic plasticity and membrane excitability driven by metabolic sensors. Here, we provide current knowledge of the role of molecular targets that constitute true metabolic/energy sensors such as AMPK, mTOR, ERK, or KATP in the development of the different phases of addiction standing out the main brain regions (ventral tegmental area, nucleus accumbens, hippocampus, and amygdala) constituting the hubs in the development of addiction. Because the available treatments show very limited effectiveness, evaluating the drug efficacy of AMPK and mTOR specific modulators opens up the possibility of testing novel pharmacotherapies for an individualized approach in drug abuse.

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Dopamine neuron-derived IGF-1 controls dopamine neuron firing, skill learning, and exploration

Cited by 55 publications

References 74 publications

Physical Activity and Brain Health

Physical Activity and Brain Health

LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury

Energy sensors in drug addiction: A potential therapeutic target

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