Leptin enhances NR2B-mediated N-methyl-d-aspartate responses via a mitogen-activated protein kinase-dependent process in cerebellar granule cells

Irving, Andrew J.; Wallace, Laurie M.; Durakoğlugil, Deniz Barlas; Harvey, Jenni

doi:10.1016/j.neuroscience.2005.11.042

Cited by 62 publications

(59 citation statements)

References 46 publications

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“…Thus, ERK activation is crucial for the synaptic depressions induced by leptin at early postnatal stages, whereas PI 3-kinase is implicated in leptin-induced hippocampal LTP in adult [29]. Our previous studies indicate that in cerebellar granule cells, leptin selectively enhances GluN2B responses via the ERK pathway [44]. Thus, it is possible that divergent signalling cascades couple leptin receptors to molecularly distinct NMDA receptors, thereby resulting in the opposing age-dependent effects of leptin on excitatory synaptic transmission.…”

Section: The Age-dependent Effects Of Leptin Involve Distinct Nmda Rementioning

confidence: 96%

Leptin regulation of hippocampal synaptic function in health and disease

Irving

Harvey

2014

Phil. Trans. R. Soc. B

102

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The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD.

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Section: The Age-dependent Effects Of Leptin Involve Distinct Nmda Rementioning

confidence: 96%

Leptin regulation of hippocampal synaptic function in health and disease

Irving

Harvey

2014

Phil. Trans. R. Soc. B

102

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“…Adipose tissue secretes a number of bioactive peptides or proteins, named adipokines. Since the first adipokine, leptin, was discovered in 1994, the adipose tissue has been granted many vital roles in addition to energy storage, making it an endocrine organ in its own right (3,4).…”

Section: Introductionmentioning

confidence: 99%

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats

Gao

Wang

Pan

et al. 2014

Arq Bras Endocrinol Metab

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Objective: Visfatin is a recently discovered adipocytokine that contributes to glucose and obesityrelated conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Materials and methods:Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Results: Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Conclusion: Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.Arq Bras Endocrinol Metab. 2014;58(1):42-7 Keywords Endocrinology; metabolic syndrome; adipocytokine RESUMO Objetivo: A visfatina é uma adipocina recentemente descoberta que contribui com as condições relacionadas à glicose e à obesidade. Até hoje, pouco se sabe da sua resposta à metformina, um agente sensibilizador de insulina, e ao exercício. Nosso objetivo foi investigar o impacto do tratamento com metformina e/ou da natação sobre a visfatina no soro e no tecido adiposo subcutâneo (TAS), tecido adiposo perirrenal (TAP) e músculo esquelético (ME) em ratos com obesidade induzida por dieta com alto teor de gordura. Materiais e métodos: Ratos Sprague-Dawley foram alimentados com uma dieta normal ou com alto teor de gordura por 16 semanas para o desenvolvimento de um modelo de obesidade. Os ratos do modelo de obesidade foram, então, randomizados para a metformina, natação ou terapia de combinação com metformina e natação, além do grupo controle de obesidade induzida por alto teor de gordura e do grupo controle normal. Cada grupo apresentava 10 ratos. Parâmetros zoométricos e glicêmicos, perfil lipídico e níveis de visfatina sérica foram avaliados no momento inicial e após seis semanas de tratamento. Os níveis de visfatina em TAS, TAP e ME foram determinados por Western Blot. Resultados: A metformina e a natação melhoraram o perfil lipídico e aumentaram a sensibilidade à insulina, com redução do peso corporal. Tanto a metformina quanto a natação levaram à regulação para baixo do...

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“…In view of this, it is feasible that leptin displays subunit-specificity in its ability to modulate NMDA receptor-dependent synaptic function and plasticity. In support of this possibility, leptin enhances NR2B-, but not NR2A-mediated responses in cerebellar granule cells [28]. It is also possible that distinct signaling cacades link leptin receptors to different combinations of NMDA receptor subunits.…”

Section: Leptin and Synaptic Plasticitymentioning

confidence: 92%

“…It is also possible that distinct signaling cacades link leptin receptors to different combinations of NMDA receptor subunits. Indeed, leptin facilitation of NR2B-mediated responses in cerebellar granule cells involves a MAPK-, but not a PI 3-kinase-, dependent process [28].…”

Section: Leptin and Synaptic Plasticitymentioning

confidence: 99%

A Tale of Two Hormones: Role of Leptin and Insulin in Hippocampal Synaptic Function

Harvey¹

2007

TONEURJ

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Abstract:It is well documented that the endocrine hormones, leptin and insulin provide signals to specific hypothalamic brain regions to regulate energy balance. However, the past decade of research has not only revealed the widespread expression of insulin and leptin receptors in the CNS, but has also identified numerous additional functions of these hormones in the brain. In particular, there is growing evidence that these hormones markedly influence hippocampal excitatory synaptic transmission as well as hippocampal synaptic plasticity. More recent studies have also identified links between dysregulation of leptin and insulin systems and the development of neurodegenerative disorders such as Alzheimer's disease. Here we review the recent evidence supporting a role for these hormones in modulating hippocampal synaptic function in health and disease.

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Leptin enhances NR2B-mediated N-methyl-d-aspartate responses via a mitogen-activated protein kinase-dependent process in cerebellar granule cells

Cited by 62 publications

References 46 publications

Leptin regulation of hippocampal synaptic function in health and disease

Leptin regulation of hippocampal synaptic function in health and disease

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats

A Tale of Two Hormones: Role of Leptin and Insulin in Hippocampal Synaptic Function

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