The Impact of Ghrelin on the Survival and Efficacy of Dopaminergic Fetal Grafts in the 6-OHDA-Lesioned Rat

Elabi, Osama F.; Dušková, Kristýna; Davies, J. S.; Lane, Emma Louise

doi:10.1016/j.neuroscience.2018.10.045

Cited by 7 publications

(9 citation statements)

References 42 publications

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“…week after the final injection of acyl-ghrelin, suggesting that it had a long-term effect to support memory. These findings are consistent with other studies reporting ghrelin-mediated increases in AHN 12,98,99 .…”

Section: Acyl-ghrelin Treatment Increases Adult Hippocampal Neurogenesissupporting

confidence: 93%

“…Ghrelin has subsequently been found to have numerous functions, including regulating gastric acid secretion and motility 3 , pancreatic cell proliferation and apoptosis 4 , sleep 5 , and cardiovascular function 6 . More recently, ghrelin has been linked to central nervous system (CNS) function, including protecting neurones 7,8 , regulating mood 9 and promoting neural plasticity via adult hippocampal neurogenesis (AHN) [10][11][12] .…”

Section: Ghrelinmentioning

confidence: 99%

See 1 more Smart Citation

Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease

Buntwal

Sassi

Morgan

et al. 2019

Trends in Endocrinology & Metabolism

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Acyl-ghrelin (AG): A Form of ghrelin that has been acylated by GOAT, which enables it to bind to GHS-R1a. Acyl-protein thioesterase 1 (APT1): An endogenous enzyme known to de-acylate acylghrelin Allosteric mechanism: Regulation of a protein or receptor independent of its active site. Brain derived neurotrophic factor (BDNF): A growth factor in the brain, involved in cell proliferation, survival, learning and memory. Bromodeoxyuridine (BrdU): A synthetic thymidine analogue, incorporated into DNA during replication. It can be used as a marker of proliferation during a specific timeframe. Butyrylcholinesterase: An enzyme that hydrolyses many different choline-based esters, but can also de-acylate acyl-ghrelin, (AG) to form unacylated ghrelin (UAG). Endogenous esterase enzyme present in the plasma known to de-acylate acyl-ghrelin. Caloric restriction (CR): A reduction of food intake (typically 30% less) in the absence of malnutrition. Calorie Restriction mimetics: endogenous or exogenous factors that mimic the effects of CR cAMP response element binding protein (CREB): A transcription factor regulating BDNF expression and important in neuronal plasticity and memory. Dentate gyrus (DG): A sub-region of the hippocampus where neurogenesis occurs. Ghrelin-O-Acyl transferase (GOAT): a member of the membrane bound O-Acyl transferase (MBOAT) family, the only enzyme known to acylate ghrelin. GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR) receptors: Glutamate receptor and ion channels responsible for fast excitatory synaptic transmission. Important for synaptic plasticity and long-term potentiation (LTP). Growth hormone secretagogue receptor (GHSR): A G-protein-coupled receptor (GPCR) also known as the ghrelin receptor. It is the only known receptor for acyl-ghrelin. GHSR-eGFP mice: genetically mutated mice that co-express green fluorescent protein (GFP) with the Growth Hormone Secretagogue Receptor (GHS-R) gene Heterodimers: A protein complex, consisting of two different proteins. Hormesis: A bi-phasic dose-response to a drug or intervention, in which a low dose produces a beneficial effect and a high dose produces a harmful effect. Long-term potentiation (LTP): An important process in memory formation, resulting in a long-term increase in the strength of electrical activity or transmission between two neurones. Neural stem progenitor cells (NSPCs): Multipotent stem cells that reside in the brain with the capacity to differentiate into any neural cell type. Novel object recognition (NOR): Behaviour test of cognitive function that requires recognising novel from familiar objects. This is a hippocampal-dependent task. Passive avoidance learning (PAL): Behaviour test that evaluate memory and learning in rodents with neurological disorders. The rodents learn to avoid an environment in which an aversive stimulus was previously delivered. Pattern separation: The ability to distinguish similar inputs into separate discrete outputs. SAMP8 mice: a naturally occurring mouse model of accelerated ageing wi...

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Section: Acyl-ghrelin Treatment Increases Adult Hippocampal Neurogenesissupporting

confidence: 93%

Section: Ghrelinmentioning

confidence: 99%

Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease

Buntwal

Sassi

Morgan

et al. 2019

Trends in Endocrinology & Metabolism

View full text Add to dashboard Cite

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“…Increased neuroblast number. [11] 7-8 weeks old male CUMS mice (on C57BL/6 background) i.p injected with acyl-ghrelin once a day for 2 weeks.…”

Section: Model and Methods Outcome Referencementioning

confidence: 99%

“…In the years since its discovery, ghrelin has been implicated in a variety of other physiological responses linked with homeostasis, including the regulation of gastric acid secretion and motility [ 3 ], pancreatic cell proliferation and apoptosis [ 4 ], sleep [ 5 ], and cardiovascular function [ 6 ]. Notably, in the central nervous system (CNS), ghrelin has been reported to regulate action potential firing [ 7 ], mitochondrial function [ 7 , 8 ], immune signalling [ 9 ], neuron survival [ 7 , 10 ], and neural stem/progenitor cell (NSPC) differentiation into adult-born hippocampal granule cells [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Acylation—A Post-Translational Tuning Mechanism Regulating Adult Hippocampal Neurogenesis

Sassi

Morgan

Davies

2022

Cells

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Adult hippocampal neurogenesis—the generation of new functional neurones in the adult brain—is impaired in aging and many neurodegenerative disorders. We recently showed that the acylated version of the gut hormone ghrelin (acyl-ghrelin) stimulates adult hippocampal neurogenesis while the unacylated form of ghrelin inhibits it, thus demonstrating a previously unknown function of unacyl-ghrelin in modulating hippocampal plasticity. Analysis of plasma samples from Parkinson’s disease patients with dementia demonstrated a reduced acyl-ghrelin:unacyl-ghrelin ratio compared to both healthy controls and cognitively intact Parkinson’s disease patients. These data, from mouse and human studies, suggest that restoring acyl-ghrelin signalling may promote the activation of pathways to support memory function. In this short review, we discuss the evidence for ghrelin’s role in regulating adult hippocampal neurogenesis and the enzymes involved in ghrelin acylation and de-acylation as targets to treat mood-related disorders and dementia.

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“…Various studies have testified that the administration of AG boosts adult hippocampal neurogenesis in healthy rodents (Zhao et al, 2014;Kent et al, 2015;Hornsby et al, 2016), dwarf rats (Li et al, 2013), in the 6-OHDA rodent model of PD, although neurogenesis was only enhanced in the non-lesioned brain hemisphere (Elabi et al, 2018), and the 5xFAD animal model of AD (Moon et al, 2014). Within the hippocampus, mice and dwarf rats were shown to possess Ki-67-positive, GHS-R1αexpressing immature neuroblasts in the granule cell layer of the DG (Moon et al, 2009b;Li et al, 2013;Hornsby et al, 2016).…”

Section: Acylated Ghrelin Induces Neurogenesis In the Hippocampusmentioning

confidence: 99%

Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease

Reich

Hölscher

2020

Front. Neurosci.

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Much thought has been given to the impact of Amyloid Beta, Tau and Alpha-Synuclein in the development of Alzheimer's disease (AD) and Parkinson's disease (PD), yet the clinical failures of the recent decades indicate that there are further pathological mechanisms at work. Indeed, besides amyloids, AD and PD are characterized by the culminative interplay of oxidative stress, mitochondrial dysfunction and hyperfission, defective autophagy and mitophagy, systemic inflammation, BBB and vascular damage, demyelination, cerebral insulin resistance, the loss of dopamine production in PD, impaired neurogenesis and, of course, widespread axonal, synaptic and neuronal degeneration that leads to cognitive and motor impediments. Interestingly, the acylated form of the hormone ghrelin has shown the potential to ameliorate the latter pathologic changes, although some studies indicate a few complications that need to be considered in the long-term administration of the hormone. As such, this review will illustrate the wide-ranging neuroprotective properties of acylated ghrelin and critically evaluate the hormone's therapeutic benefits for the treatment of AD and PD.

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The Impact of Ghrelin on the Survival and Efficacy of Dopaminergic Fetal Grafts in the 6-OHDA-Lesioned Rat

Cited by 7 publications

References 42 publications

Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease

Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease

Ghrelin Acylation—A Post-Translational Tuning Mechanism Regulating Adult Hippocampal Neurogenesis

Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease

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