Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid

Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

doi:10.1016/j.peptides.2015.07.005

Cited by 40 publications

(34 citation statements)

References 38 publications

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“…reported that peripheral ghrelin injections rescue memory deficits, prevent microgliosis and neuronal or synaptic degeneration in an AD mouse model induced by intrahippocampal injections of Aβ. These results have been confirmed with a central infusion of acyl ghrelin, which improved memory function, hippocampal AMPK activation and decreased Aβ deposition . In cultured hippocampal neurones, ghrelin ameliorated Aβ‐induced cell death by preventing mitochondrial dysfunction …”

Section: Introductionmentioning

confidence: 64%

Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1‐40) administration in mice

Santos

Stark

Rial

et al. 2017

J Neuroendocrinology

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Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In the present study, we used ghrelin knockout (KO) and their wild-type littermates to test whether or not endogenous ghrelin is protective in a mouse model of AD, in which human amyloid β peptide 1-40 (Aβ ) was injected into the lateral ventricles i.c.v. Recognition memory, using the novel object recognition task, was significantly impaired in ghrelin KO mice and after i.c.v. Aβ treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Spatial orientation, as assessed by the Y-maze task, was also significantly impaired in ghrelin KO mice and after i.c.v. Aβ treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Ghrelin KO mice had deficits in olfactory discrimination; however, neither i.c.v. Aβ treatment, nor acyl ghrelin injections affected olfactory discrimination. We used stereology to show that ghrelin KO and Aβ increased the total number of glial fibrillary acidic protein expressing astrocytes and ionised calcium-binding adapter expressing microglial in the rostral hippocampus. Finally, Aβ blocked long-term potentiation induced by high-frequency stimulation and this effect could be acutely blocked with co-administration of acyl ghrelin. Collectively, our studies demonstrate that ghrelin deletion affects memory performance and also that acyl ghrelin treatment may delay the onset of early events of AD. This supports the idea that acyl ghrelin treatment may be therapeutically beneficial with respect to restricting disease progression in AD.

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Section: Introductionmentioning

confidence: 64%

Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1‐40) administration in mice

Santos

Stark

Rial

et al. 2017

J Neuroendocrinology

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“…Central intracerebroventricular (ICV) administration of ghrelin ameliorated the cognitive dysfunction and neurodegeneration induced by intrahippocampal injections of amyloid-β oligomers in mice and rats, with associated improvements in cerebral glucose metabolism [185,186]. Oral administration of the ghrelin agonist LY444711 similarly improved cognition and reduced cerebral inflammation and beta-amyloid levels in the APP-SwDI genetic mouse model of AD (APP-Swedish K760N/M671L, Dutch E693Q and Iowa D694N mouse) [187,188].…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

Therapeutic Potential of Targeting the Ghrelin Pathway

Colldén

Tschöp

Müller

2017

IJMS

124

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Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems’ metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

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“…AG binds to the growth hormone secretagogue receptor 1a isoform (GHSR1) [25], which is expressed in the cerebral cortex in vivo [27], as well as in dissociated cortical neurons [23], and is responsible for some of the central and peripheral effects of ghrelin [31]. As recently reported, ghrelin enhances synaptic plasticity [26], memory consolidation [32], and adult neurogenesis [33, 34]. Here, we show that ghrelin improves synaptic recovery in an in vitro model of postanoxic encephalopathy consisting of cultured neuronal networks exposed to severe hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy

et al. 2015

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Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2 lowered from 150 to 20 mmHg) during 6 h in 55 cultures. Three hours after restoration of normoxia, half of the cultures were treated with ghrelin for 24 h, while the other, non-supplemented, were used as a control. All cultures were processed immunocytochemically for detection of the synaptic marker synaptophysin. We observed that hypoxia led to drastic decline of the number of synapses, followed by some recovery after return to normoxia, but still below the prehypoxic level. Additionally, synaptic vulnerability was selective: large- and small-sized neurons were more susceptible to synaptic damage than the medium-sized ones. Ghrelin treatment significantly increased the synapse density, as compared with the non-treated controls or with the prehypoxic period. The effect was detected in all neuronal subtypes. In conclusion, exogenous ghrelin has a robust impact on the recovery of cortical synapses after hypoxia. It raises the possibility that ghrelin or its analogs may have a therapeutic potential for treatment of postanoxic encephalopathy.

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Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid

Cited by 40 publications

References 38 publications

Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1‐40) administration in mice

Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1‐40) administration in mice

Therapeutic Potential of Targeting the Ghrelin Pathway

Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy

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