Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function

Saunders, Christine; Siuta, Michael; Robertson, Sabrina D.; Davis, Adeola R.; Sauer, Jennifer; Matthies, Heinrich J.G.; Gresch, Paul J.; Airey, David; Lindsley, Craig W.; Schetz, John A.; Niswender, Kevin D.; Veenstra‐VanderWeele, Jeremy; Galli, Aurelio

doi:10.1016/j.neuint.2013.09.015

Cited by 15 publications

(13 citation statements)

References 72 publications

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“…Thus, we could speculate that the alteration of p-AKT/AKT induced by BDNF overexpression under the pathological circumstances was linked with the change of NeuN, 5-HT as well as GAP-43. These were supported from other literatures which indicated BDNF-AKT signal as crucial pathway in pulmonary injury, traumatic brain injury and cerebral ischemia [52][53][54][55][56][57].…”

Section: Bdnf Overexpression May Lead To Thermal Hyperalgesiasupporting

confidence: 83%

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

et al. 2016

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Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

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Section: Bdnf Overexpression May Lead To Thermal Hyperalgesiasupporting

confidence: 83%

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

et al. 2016

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“…2). Notably, a novel role for AKT has been found in maintaining neuronal serotonin (5-HT) receptor function (33). In addition, 5-HT activates the PI3K/AKT signaling pathway in several cancer cell lines (34).…”

Section: Relationship Between Cell Surface Gpcrs and Pi3k/akt Signalimentioning

confidence: 99%

PI3K/AKT signaling mediated by G protein-coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

Nakano

Matsuda

Ichimura

et al. 2016

International Journal of Molecular Medicine

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Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. Motor deficits in PD are due mostly to the progressive loss of nigrostriatal dopaminergic neurons. Neuroprotection of functional neurons is of significance in the treatment of PD. G protein‑coupled receptors (GPCRs) have been implicated in the neuroprotection against PD through the survival of dopaminergic neurons. In addition, phosphatidyl‑inositol‑3‑kinase (PI3K)/AKT signaling has also been demonstrated to be neuroprotective. Knowledge of the mechanisms involved in this cellular protection could be critical for developing treatments to prevent this neurodegenerative disorder. In this review, we highlight the protective roles of the PI3K/AKT signaling pathway in the function of representative serotonin GPCRs. Particular attention is given to the molecular mechanisms of this pathway proposed to explain the favorable effects of food ingredients against neurodegenerative disease.

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“…Recent discoveries suggest that central serotonin (5-HT) signaling contributes to insulin resistance (IR) in mice [1] and that peripheral 5-HT participates in the regulation of insulin secretion by human islet [2]. Fourteen 5-HT receptors are expressed in human islets [2], which highlights the importance of examining how different 5-HT receptors mediate the effects of 5-HT on islet hormone secretion in humans.…”

Section: Introduction ▼mentioning

confidence: 99%

Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men

Tikkanen

Saukkonen

Fex

et al. 2016

Exp Clin Endocrinol Diabetes

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Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation ( Q20*) heterozygote carrier (=11) or not (=57). Serum levels of glucose, insulin, and glucagon were measured in a 5 h oral glucose tolerance test using a 75 g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion.

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Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function

Cited by 15 publications

References 72 publications

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

PI3K/AKT signaling mediated by G protein-coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men

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