scholarly journals The orexigenic hormone acyl-ghrelin increases adult hippocampal neurogenesis and enhances pattern separation

2015 ◽  
Vol 51 ◽  
pp. 431-439 ◽  
Author(s):  
Brianne A. Kent ◽  
Amy L. Beynon ◽  
Amanda K.E. Hornsby ◽  
Pedro Bekinschtein ◽  
Timothy J. Bussey ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pattern Separation ◽  
Acyl Ghrelin

scholarly journals Circulating unacylated-ghrelin impairs hippocampal neurogenesis and memory in mice and is altered in human Parkinson's disease dementia

2018 ◽  
Author(s):  
Amanda K E Hornsby ◽  
Vanessa V Santos ◽  
Fionnuala Johnston ◽  
Luke D Roberts ◽  
Romana Stark ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Plasticity ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Unexpected Finding ◽  
Unacylated Ghrelin ◽  
Memory Impairments ◽  
Acyl Ghrelin

Blood-borne factors regulate adult hippocampal neurogenesis (AHN) and cognition in mammals, albeit via mechanisms that are poorly understood. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in GOAT-/- mice that lack acyl-ghrelin (AG) but have high levels of UAG, were rescued by treatment with AG. This unexpected finding suggests that the post-translational acylation of ghrelin is an important modulator of neurogenesis and memory in adult mammals. To determine whether this paradigm is relevant to humans we analysed circulating AG:UAG levels in Parkinson's disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients and healthy controls. Uniquely, the ratio of plasma AG:UAG was reduced in the PDD cohort and correlated with cognitive performance. Our results identify UAG as a novel regulator of neurogenesis and cognition, and AG:UAG as a circulating diagnostic biomarker of dementia. The findings extend our understanding of adult brain plasticity regulation by circulating factors and suggest that manipulating the post-translational acylation of plasma ghrelin may offer therapeutic opportunities to ameliorate cognitive decline.

Investigating the role of the ghrelin axis in cognitive decline and dementia

2021 ◽  
Author(s):  
◽  
Martina Sassi
Keyword(s):  
Mouse Model ◽  
Cognitive Decline ◽  
Young Animal ◽  
Active Form ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Tg2576 Mouse ◽  
Brain Functions ◽  
Acyl Ghrelin ◽  
The Brain

Ghrelin is a 28-amino acid hormone that is generated in a wide number of tissues. Its active form, acyl-ghrelin is able to bind to its receptor GHS-R and exert a variety of functions. In the brain, acyl-ghrelin has been associated with neuroprotection, improved memory and adult hippocampal neurogenesis (AHN). However, the mechanisms controlling acyl-ghrelin-mediated AHN are still unknown. To elucidate this process, different markers of neurogenesis were assessed in a mouse model in which GHS-R+ neurones were ablated specifically from the rostral DG of the hippocampus (rDG), showing that rDG GHS-R+ neurones are essential for maintaining AHN. Acyl-ghrelin has also been shown to prevents the damage caused by neurodegeneration, at least in young animal models of disease. In this thesis, we demonstrated that in the geriatric Tg2576 mouse model of Alzheimer’s disease, acyl-ghrelin maintained an effect on β-amyloid (Aβ) plaques in the hippocampus, promoting a reduction of the Aβ plaques size in AD-like mouse model compared to WT mice. Collectively, research findings highlight the importance of circulating acyl-ghrelin in the brain. However, ghrelin exists in two distinct forms and acyl-ghrelin can be enzymatically modified to the ‘inactive' unacylated-ghrelin (UAG) by acyl-protein thioesterase 1 (APT1). Preventing APT1 mediated de-acylation and increasing acyl-ghrelin bio-availability may prevent the damage caused by neurodegeneration. Unpublished data from our group suggest that PalmostatinB, an APT1 inhibitor, increases levels of acyl-ghrelin in macrophage cells (that naturally produce ghrelin). Therefore, this and other APT1 inhibitors may be considered possible therapeutic agents for the treatment of cognitive decline and diseases associated with dementia. We confirmed that, among several APT1 inhibitors, PalmostatinB is able to increase the level of acyl-ghrelin in vitro. However, further research is warranted into APT1 inhibitors as a novel therapeutic approach to treating cognitive decline and dementia. Together, the data in this thesis support a role for the ghrelinergic system components in modulating brain functions.

scholarly journals Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 638 ◽  
Author(s):  
Curie Kim ◽  
Ana Margarida Pinto ◽  
Claire Bordoli ◽  
Luke Patrick Buckner ◽  
Polly Charlotte Kaplan ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Central Obesity ◽  
Human Study ◽  
Energy Restriction ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pattern Separation ◽  
Intermittent Fasting ◽  
Ageing Population ◽  
Cognitive Improvement

Adult neurogenesis, the generation of new neurons throughout life, occurs in the subventricular zone of the dentate gyrus in the human hippocampal formation. It has been shown in rodents that adult hippocampal neurogenesis is needed for pattern separation, the ability to differentially encode small changes derived from similar inputs, and recognition memory, as well as the ability to recognize previously encountered stimuli. Improved hippocampus-dependent cognition and cellular readouts of adult hippocampal neurogenesis have been reported in daily energy restricted and intermittent fasting adult mice. Evidence that nutrition can significantly affect brain structure and function is increasing substantially. This randomized intervention study investigated the effects of intermittent and continuous energy restriction on human hippocampal neurogenesis-related cognition, which has not been reported previously. Pattern separation and recognition memory were measured in 43 individuals with central obesity aged 35–75 years, before and after a four-week dietary intervention using the mnemonic similarity task. Both groups significantly improved pattern separation (P = 0.0005), but only the intermittent energy restriction group had a significant deterioration in recognition memory. There were no significant differences in cognitive improvement between the two diets. This is the first human study to investigate the association between energy restriction with neurogenesis-associated cognitive function. Energy restriction may enhance hippocampus-dependent memory and could benefit those in an ageing population with declining cognition. This study was registered on ClinicalTrials.gov (NCT02679989) on 11 February 2016.

Adult Hippocampal Neurogenesis, Pattern Separation, and Generalization

2016 ◽  
Author(s):  
Kristen C. Klemenhagen ◽  
Franklin R. Schneier ◽  
Abby J. Fyer ◽  
H. Blair Simpson ◽  
René Hen
Keyword(s):  
Anxiety Disorder ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pattern Separation ◽  
Post Traumatic Stress ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Evidence Based Treatments ◽  
Post Traumatic ◽  
Pathological Anxiety

Almost one-third of adult Americans will have an anxiety disorder in their lifetime, with enormous personal, societal, and financial costs. Among the most disabling of these disorders are post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social anxiety disorder, generalized anxiety disorder, and panic disorder. Although there are evidence-based treatments for these disorders, as many as 50% of patients do not respond, and there is a considerable need for new therapies. This chapter proposes that the excessive generalization seen in patients with pathological anxiety is due to impaired hippocampal functioning, specifically a deficit in the neural process of pattern separation, which relies upon the dentate gyrus and is sensitive to neurogenesis. Preclinical findings indicate that stimulating DG neurogenesis improves pattern separation and reduces anxiety behaviors in mice. As a result the authors hypothesize that pharmacological or environmental manipulations aimed at stimulating neurogenesis will be beneficial for the treatment of anxiety disorders.

scholarly journals Adult hippocampal neurogenesis shapes adaptation and improves stress response: a mechanistic and integrative perspective

2021 ◽  
Author(s):  
A. Surget ◽  
C. Belzung
Keyword(s):  
Stress Response ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pattern Separation ◽  
Brain Areas ◽  
Functional Involvement ◽  
Different Dimensions ◽  
Stressful Experiences ◽  
The Brain

AbstractAdult hippocampal neurogenesis (AHN) represents a remarkable form of neuroplasticity that has increasingly been linked to the stress response in recent years. However, the hippocampus does not itself support the expression of the different dimensions of the stress response. Moreover, the main hippocampal functions are essentially preserved under AHN depletion and adult-born immature neurons (abGNs) have no extrahippocampal projections, which questions the mechanisms by which abGNs influence functions supported by brain areas far from the hippocampus. Within this framework, we propose that through its computational influences AHN is pivotal in shaping adaption to environmental demands, underlying its role in stress response. The hippocampus with its high input convergence and output divergence represents a computational hub, ideally positioned in the brain (1) to detect cues and contexts linked to past, current and predicted stressful experiences, and (2) to supervise the expression of the stress response at the cognitive, affective, behavioral, and physiological levels. AHN appears to bias hippocampal computations toward enhanced conjunctive encoding and pattern separation, promoting contextual discrimination and cognitive flexibility, reducing proactive interference and generalization of stressful experiences to safe contexts. These effects result in gating downstream brain areas with more accurate and contextualized information, enabling the different dimensions of the stress response to be more appropriately set with specific contexts. Here, we first provide an integrative perspective of the functional involvement of AHN in the hippocampus and a phenomenological overview of the stress response. We then examine the mechanistic underpinning of the role of AHN in the stress response and describe its potential implications in the different dimensions accompanying this response.

Sign in / Sign up

Export Citation Format

Share Document