Cognitive improvement by acute growth hormone is mediated by NMDA and AMPA receptors and MEK pathway

Ramis, Margarita; Sarubbo, Fiorella; Solà, Jéssica; Aparicio, Sara; Garau, Celia; Miralles, Antonio; Esteban, Susana

doi:10.1016/j.pnpbp.2013.04.005

Cited by 27 publications

(24 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…39,41 Moreover, episodic-like memory was assessed by the novel object recognition test, which deals with the natural ability of animals to explore novelties. 32 Consistent with previous observations, 6,7,29,42 aged control rats showed an impairment of cognitive abilities, including working memory in the radial maze, episodic-like memory on the novel object recognition test and spatial learning on the Barnes maze test. Nevertheless, a significant improvement of these memory tasks was observed after treatment with the higher dose of α-tocopherol analyzed.…”

Section: Discussionsupporting

confidence: 88%

“…6,7,29 The maze (Panlab, S.L., Spain) was set in an experimental room with different visual cues which were not moved during the whole experiment as animal's reference points. Animals were allowed to visit the arms to obtain food pellets until the This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

Section: Radial Maze Taskmentioning

confidence: 99%

“…The procedure consists of three phases: habituation, familiarization, and test phase. 29 In the habituation phase, each animal is allowed freely exploring the open field in the absence of objects for 10 min, daily, during four consecutive days. On day 5, each animal was placed in the apparatus and allowed to explore for 1 min for re-habituation.…”

Section: Novel Object Recognition Testmentioning

confidence: 99%

See 2 more Smart Citations

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats

Ramis

Sarubbo

Terrasa

et al. 2016

Rejuvenation Research

Self Cite

View full text Add to dashboard Cite

Limiting enzymes in the synthesis of brain monoamines seems to be susceptible to oxidative damage, one of the most important factors in aging. It has been suggested that the use of anti-oxidants can reduce the rate of free radical production related with aging and the associated damage. Therefore, this study aims to analyze the effects of the chronic treatments with the anti-oxidant α-tocopherol (vitamin E) on central monoamines (high-performance liquid chromatography [HPLC] analysis) mediating cognitive functions, as well as on the evaluation of memory and motor abilities in old rats measured by radial maze, Barnes maze, novel object recognition test, and rotarod test. Results show that α-tocopherol significantly increased in a dose- and/or time-dependent manner the synthesis rate and the levels of monoaminergic neurotransmitters (serotonin, dopamine, and noradrenaline) in the hippocampus and striatum, brain regions involved in memory processing and motor coordination. These positive neurochemical effects, largely due to an increased activity of the limiting enzymes in monoamines synthesis, tryptophan hydroxylase and tyrosine hydroxylase, were accompanied by an improvement in cognitive and motor abilities in old rats. Altogether these findings suggest that α-tocopherol exhibits neuroprotective actions in old rats; thus, diets with α-tocopherol might represent a promising strategy to mitigate or delay the cognitive and motor decline associate with aging and related-diseases.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Radial Maze Taskmentioning

confidence: 99%

Section: Novel Object Recognition Testmentioning

confidence: 99%

See 1 more Smart Citation

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats

Ramis

Sarubbo

Terrasa

et al. 2016

Rejuvenation Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, it is conceivable that secondary effects of GH deficiency are more important for the cognitive deficits than impaired brain GHR signaling per se. Several studies have shown that IGF-1 signaling has neuroprotective and neurodevelopmental effects and also influences cognitive processes (Miltiadous et al 2011;O'Kusky and Ye 2012;Aberg et al 2006;Witty et al 2013;Le Greves et al 2005;Molina et al 2013;Sonntag et al 2013;Ramis et al 2013). However, the wide distribution of GH-responsive cells in areas involved in mechanisms of learning and memory, as well as in emotional/motivational processes, provides neuroanatomical evidence that GH signaling may directly affect cognitive processes and the expression of behaviors, independently of changes in IGF-1 circulating levels.…”

Section: Possible Functional Implications Of Gh-responsive Cells In Tmentioning

confidence: 99%

Distribution of growth hormone-responsive cells in the mouse brain

et al. 2016

View full text Add to dashboard Cite

Growth hormone (GH) exerts important biological effects primarily related to growth and metabolism. However, the role of GH signaling in the brain is still elusive. To better understand GH functions in the brain, we mapped the distribution of GH-responsive cells and identified the receptors involved in GH central effects. For this purpose, mice received an acute intraperitoneal challenge with specific ligands of the GH receptor (mouse GH), prolactin receptor (prolactin) or both receptors (human GH), and their brains were subsequently processed immunohistochemically to detect the phosphorylated form of STAT5 (pSTAT5). GH induced pSTAT5 immunoreactivity in neurons, but not in astroglial cells of numerous brain regions, including the cerebral cortex, nucleus accumbens, hippocampus, septum and amygdala. The most prominent populations of GH-responsive neurons were located in hypothalamic areas, including several preoptic divisions, and the supraoptic, paraventricular, suprachiasmatic, periventricular, arcuate, ventromedial, dorsomedial, tuberal, posterior and ventral premammillary nuclei. Interestingly, many brainstem structures also exhibited GH-responsive cells. Experiments combining immunohistochemistry for pSTAT5 and in situ hybridization for GH and prolactin receptors revealed that human GH induced pSTAT5 in most, but not all, brain regions through both prolactin and GH receptors. Additionally, males and females exhibited a similar number of GH-responsive cells in forebrain structures known to be sexually dimorphic. In summary, we found GH-responsive cells primarily distributed in brain regions implicated in neurovegetative, emotional/motivational and cognitive functions. Our findings deepen the understanding of GH signaling in the brain and suggest that central GH signaling is likely more ample and complex than formerly recognized.

show abstract

“…The apparatus was cleaned with ethanol solution between trials. Rats movements were monitored via a digital video tracking system (LE 8300 with software SEDACOM v 1.3, Panlab, SL, Barcelona, Spain) (for further descriptions, see Esteban et al 2010a, b;Ramis et al 2013). Tests were performed before chronic treatments (initial test) and after chronic treatments.…”

Section: Memory Behavioral Testmentioning

confidence: 99%

Improving effect of chronic resveratrol treatment on central monoamine synthesis and cognition in aged rats

Sarubbo

Ramis

Aparicio

et al. 2015

AGE

View full text Add to dashboard Cite

Resveratrol is a polyphenol exhibiting antioxidant and neuroprotective effects in neurodegenerative diseases. However, neuroprotective properties during normal aging have not been clearly demonstrated. We analyzed the in vivo effects of chronic administration of resveratrol (20 mg/kg/day for 4 weeks) in old male rats (Wistar, 20 months), on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities which mediate central monoaminergic neurotransmitters synthesis, and besides, on hippocampal-dependent working memory test (radial maze). Our results show an age-related decline in neurochemical parameters that were reversed by resveratrol administration. The resveratrol treatment enhances serotonin (5-HT) levels in pineal gland, in hippocampus, and in striatum, and those of noradrenaline (NA) in hippocampus and also dopamine (DA) in striatum. These changes were largely due to an increased activity of TPH-1 (463 % in pineal gland), TPH-2 (70-51 % in hippocampus and striatum), and TH (150-36 % in hippocampus and striatum).Additionally, the observed hippocampal effects correlate with a resveratrol-induced restorative effect on working memory (radial maze). In conclusion, this study suggests resveratrol treatment as a restoring therapy for the impaired cognitive functions occurring along normal aging process, by preventing 5-HT, DA, and NA neurotransmission decline.

show abstract

Cognitive improvement by acute growth hormone is mediated by NMDA and AMPA receptors and MEK pathway

Cited by 27 publications

References 61 publications

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats

Distribution of growth hormone-responsive cells in the mouse brain

Improving effect of chronic resveratrol treatment on central monoamine synthesis and cognition in aged rats

Contact Info

Product

Resources

About