Insulin signaling in the central nervous system: Learning to survive

Heide, Lars P. van der; Ramakers, G.J.A.; Smidt, Marten P.

doi:10.1016/j.pneurobio.2006.06.003

Cited by 373 publications

(294 citation statements)

References 166 publications

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“…The NTRK3 gene encodes a membrane-bound receptor that phosphorylates intracellular transducers, including IRS2 (43). The downstream influences of IRS2 can manifest via activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway (44). AKT signaling affects synaptic plasticity, axonal development, amygdala-dependent learning, and behavioral responses to stress (45,46).…”

Section: Resultsmentioning

confidence: 99%

Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates

Fox

Oler

Shelton

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Children with anxious temperament (AT) are particularly sensitive to new social experiences and have increased risk for developing anxiety and depression. The young rhesus monkey is optimal for studying the origin of human AT because it shares with humans the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning. In vivo imaging in young monkeys demonstrated that central nucleus of the amygdala (Ce) metabolism is relatively stable across development and predicts AT. Transcriptome-wide gene expression, which reflects combined genetic and environmental influences, was assessed within the Ce. Results support a maladaptive neurodevelopmental hypothesis linking decreased amygdala neuroplasticity to early-life dispositional anxiety. For example, high AT individuals had decreased mRNA expression of neurotrophic tyrosine kinase, receptor, type 3 (NTRK3). Moreover, variation in Ce NTRK3 expression was inversely correlated with Ce metabolism and other AT-substrates. These data suggest that altered amygdala neuroplasticity may play a role the early dispositional risk to develop anxiety and depression.positron-emission tomography | microarray | brain imaging T he ability to identify brain mechanisms underlying the risk during childhood for developing anxiety and depression is critical for establishing novel early-life interventions aimed at preventing the chronic and debilitating outcomes associated with these common illnesses. To this end, we have optimized a model of anxious temperament (AT), the conserved at-risk phenotype, in young developing rhesus monkeys (1-4). The rhesus monkey is ideal for studying the origin of human AT because these species share the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning (5-10). Importantly, the rhesus developmental model bridges the critical gap between human psychopathology and rodent models, allowing for translation to humans by using in vivo imaging measures and translation to rodents by using ex vivo molecular methods. Thus, the unique hypotheses that can be generated from the rhesus model are invaluable in guiding both imaging studies in children and mechanistic efforts in rodents.Of particular relevance to the AT rhesus model is the relatively recent evolutionary divergence between rhesus monkeys and humans (25 million years) compared with rodents and humans (70 million years) (5). This evolutionary closeness is reflected in the species' similarities in social and emotional behaviors. These homologies, instantiated in their conserved genetic and neural systems, underlie the ability of both humans and rhesus monkeys to form and maintain the relationships necessary for living in complex social environments. In this regard, the experience of anxiety has evolved in primates to motivate the formation of long-lasting attachment bonds that serve to increase security and group cohesion. The comparable rearing practices shared by these species (e.g., close mother-infant bonding) promote early social/emotional le...

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Section: Resultsmentioning

confidence: 99%

Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates

Fox

Oler

Shelton

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…These findings on the role of insulin in regulating neuronal functions provides the opportunity to define how internal metabolic state may modulate chemosensory neuron functions. As insulin signaling has been implicated in neuronal plasticity in other organisms [171,172], it will be interesting to explore whether insulin acts via similar feedback mechanisms to regulate neuronal function.…”

Section: Modulation Of Chemosensory Behaviorsmentioning

confidence: 99%

Generation and modulation of chemosensory behaviors in C. elegans

Sengupta

2007

Pflugers Arch - Eur J Physiol

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C. elegans recognizes and discriminates among hundreds of chemical cues using a relatively compact chemosensory nervous system. Chemosensory behaviors are also modulated by prior experience and contextual cues. Because of the facile genetics and genomics possible in this organism, C. elegans provides an excellent system in which to explore the generation of chemosensory behaviors from the level of a single gene to the motor output. This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans.

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“…53 IGF-1 and insulin act through the insulin/insulin receptor (IR) signaling pathway, the activation of which supports neuronal survival and brain plasticity. 73 The neuroprotective effects of the IR pathway are well documented, 34,74 but it has also been shown that insulin injection could impair brain function. 75,76 Also, a recent paper has reportd findings similar to ours, namely, that insulin injection eliminates the beneficial effects of exercise as shown on the Morris water maze test, and it was suggested that this could be a result of the IR signaling on N-methyl-D-aspartate receptors.…”

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confidence: 99%

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

Koltai

Zhao

Lacza

et al. 2011

Rejuvenation Research

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We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5 mg/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO 2 max]) on neurogenesis, DNA damage/repair, and sirtuin content in the hippocampus of young (3 months old) and old (26 months old) rats. Exercise improved the spatial memory of the old group, but IGF-1 supplementation eliminated this effect. An age-associated decrease in neurogenesis was attenuated by exercise and IGF-1 treatment. Aging increased the levels of 8-oxo-7,8-dihydroguanine (8-oxoG) and the protein Ku70, indicating the role of DNA damage in age-related neuropathology. Acetylation of 8-oxoguanine DNA glycosylase (OGG1) was detected in vivo, and this decreased with aging. However, in young animals, exercise and IGF-1 treatment increased acetylated (ac) OGG1 levels. Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large increase in acetylated lysine residues in the hippocampus. On the other hand, SIRT3 increased with aging. Exercise-induced neurogenesis might not be a causative factor of increased spatial memory, because IGF-1 plus exercise can induce neurogenesis in the hippocampus of older rats. Data revealed that the age-associated increase in 8-oxoG levels is due to decreased acetylation of OGG1. Age-associated decreases in SIRT1 and the associated increase in lysine acetylation, in the hippocampus, could have significant impact on function and thus, could suggest a therapeutic target.

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Insulin signaling in the central nervous system: Learning to survive

Cited by 373 publications

References 166 publications

Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates

Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates

Generation and modulation of chemosensory behaviors in C. elegans

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

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