scholarly journals Treadmill Exercise Ameliorates Adult Hippocampal Neurogenesis Possibly by Adjusting the APP Proteolytic Pathway in APP/PS1 Transgenic Mice

2021 ◽  
Vol 22 (17) ◽  
pp. 9570
Author(s):  
Haizhen Yu ◽  
Chenfei Zhang ◽  
Jie Xia ◽  
Bo Xu
Keyword(s):  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Treadmill Exercise ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Memory Capacity ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Related Factors ◽  
Proteolytic Pathway

Alzheimer’s disease (AD) is a neurodegenerative disorder known to cause cognitive impairment among the elderly worldwide. Although physical exercise-induced adult hippocampal neurogenesis (AHN) improves cognition, understanding its underlying molecular mechanisms requires further investigation using AD mouse models. In this present work, we subjected amyloid precursor protein (APP)/PS1 mice to a 12-week aerobic treadmill exercise to investigate AHN and its potential mechanisms. We divided 3-month-old littermates wild-type and APP/PS1 transgenic male mice into four groups, and the exercise groups performed 12-week treadmill exercise. Next, we evaluated the influence of treadmill exercise on learning and memory capacity, AHN, and APP proteolytic pathway-related factors. As per our results, the treadmill exercise was able to improve the hippocampal microenvironment in APP/PS1 mice probably by regulating various neurotrophic factors and secretases resulting in APP cleavage through a non-amyloidogenic pathway, which seems to further promote new cell proliferation, survival, and differentiation, enhancing hippocampal neurogenesis. All of these effects ameliorate learning and memory capacity. This study provides a theoretical and experimental basis for understanding AHN in an AD mouse model, which is beneficial for preventing and treating AD.

scholarly journals Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mark I. Ransome ◽  
Thibault Renoir ◽  
Anthony J. Hannan
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Adult Neurogenesis ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Transgenic Animal ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

Huntington’s disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidated. There are a range of different brain regions, including the cerebral cortex and striatum, known to be affected in HD, with evidence for hippocampal dysfunction accumulating in recent years. In this review we will focus on hippocampal abnormalities, in particular, deficits of adult neurogenesis. We will discuss potential molecular mechanisms mediating disrupted hippocampal neurogenesis, and how this deficit of cellular plasticity may in turn contribute to specific cognitive and affective symptoms that are prominent in HD. The generation of transgenic animal models of HD has greatly facilitated our understanding of disease mechanisms at molecular, cellular, and systems levels. Transgenic HD mice have been found to show progressive behavioral changes, including affective, cognitive, and motor abnormalities. The discovery, in multiple transgenic lines of HD mice, that adult hippocampal neurogenesis and synaptic plasticity is disrupted, may help explain specific aspects of cognitive and affective dysfunction. Furthermore, these mouse models have provided insight into potential molecular mediators of adult neurogenesis deficits, such as disrupted serotonergic and neurotrophin signaling. Finally, a number of environmental and pharmacological interventions which are known to enhance adult hippocampal neurogenesis have been found to have beneficial affective and cognitive effects in mouse models, suggesting common molecular targets which may have therapeutic utility for HD and related diseases.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

scholarly journals Deltamethrin Exposure Inhibits Adult Hippocampal Neurogenesis and Causes Deficits in Learning and Memory in Mice

2020 ◽  
Vol 178 (2) ◽  
pp. 347-357
Author(s):  
Muhammad M Hossain ◽  
Abdelmadjid Belkadi ◽  
Sara Al-Haddad ◽  
Jason R Richardson
Keyword(s):  
Object Recognition ◽  
Learning And Memory ◽  
Water Maze ◽  
Cellular Proliferation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Novel Object Recognition ◽  
Short Term ◽  
Novel Object ◽  
Short Term Exposure

Abstract Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3 mg/kg every 3 days for 1 month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure significantly decreased bromodeoxyuridine (BrdU)-positive cells (39%) and Ki67+ cells (47%) in the DG of the hippocampus, indicating decreased cellular proliferation. In addition, deltamethrin-treated mice exhibited a 44% decrease in nestin-expressing neural progenitor cells and a 38% reduction in the expression of doublecortin (DCX), an early neuronal differentiation marker. Furthermore, deltamethrin-exposed mice exhibited a 25% reduction in total number of granule cells in the DG. These findings indicate that relatively short-term exposure to deltamethrin causes significant deficits in hippocampal neurogenesis that is associated with impaired learning and memory.

scholarly journals Ghrelin directly stimulates adult hippocampal neurogenesis: implications for learning and memory

2013 ◽  
pp. 781-789 ◽  
Author(s):  
Endan Li ◽  
Hyunju Chung ◽  
Yumi Kim ◽  
Dong Hyun Kim ◽  
Jong Hoon Ryu ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice

2021 ◽  
Author(s):  
Thomas H Lee ◽  
Ahadullah ◽  
Brian R Christie ◽  
Kangguang Lin ◽  
Parco Ming-fai Siu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Physical Exercise ◽  
Learning And Memory ◽  
Long Term Potentiation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Antidepressant Effect ◽  
Spine Density ◽  
Diabetic Mice ◽  
Antidiabetic Effect

AbstractAdministration of exercise mimetic drugs could be a novel therapeutic approach to combat comorbid neurodegeneration and metabolic syndromes. Adiponectin is an adipocyte-secreted hormone. In addition to its antidiabetic effect, adiponectin mediates the antidepressant effect of physical exercise associated with adult hippocampal neurogenesis. The antidiabetic effect of the adiponectin receptor agonist AdipoRon has been demonstrated, but its potential pro-cognitive and neurotrophic effects in the hippocampus under diabetic condition are still unclear. This study reported that chronic AdipoRon treatment for 2 weeks improved hippocampal-dependent spatial recognition memory in streptozotocin-induced diabetic mice. Besides, AdipoRon treatment increased progenitor cell proliferation and neuronal differentiation in the hippocampal dentate gyrus (DG) of diabetic mice. Furthermore, AdipoRon treatment significantly increased dendritic complexity, spine density, and N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) in the dentate region, and increased BDNF levels in the DG of diabetic mice. AdipoRon treatment activated AMPK/PGC-1α signalling in the DG, whereas increases in cell proliferation and LTP were not observed when PGC-1α signalling was pharmacologically inhibited. In sum, chronic AdipoRon treatment partially mimics the benefits of physical exercise for learning and memory and hippocampal neuroplasticity in the diabetic brain. The results suggested that AdipoRon could be a potential physical exercise mimetic to improve hippocampal plasticity and hence rescue learning and memory impairment typically associated with diabetes.

scholarly journals New Insights Into the Role of Aberrant Hippocampal Neurogenesis in Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Chen ◽  
Fuchao Chen ◽  
Yue Wu ◽  
Benhong Zhou
Keyword(s):  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Future Directions ◽  
The Past ◽  
The Central Nervous System ◽  
Spontaneous Recurrent Seizures ◽  
Patients With Epilepsy

Data accumulated over the past four decades have confirmed that adult hippocampal neurogenesis (HN) plays a key role in the wide spectrum of hippocampal pathology. Epilepsy is a disorder of the central nervous system characterized by spontaneous recurrent seizures. Although neurogenesis in persistent germinative zones is altered in the adult rodent models of epilepsy, the effects of seizure-induced neurogenesis in the epileptic brain, in terms of either a pathological or reparative role, are only beginning to be explored. In this review, we described the most recent advances in neurogenesis in epilepsy and outlooked future directions for neural stem cells (NSCs) and epilepsy-in-a-dish models. We proposed that it may help in refining the underlying molecular mechanisms of epilepsy and improving the therapies and precision medicine for patients with epilepsy.

scholarly journals Comparison of Adult Hippocampal Neurogenesis and Susceptibility to Treadmill Exercise in Nine Mouse Strains

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jong Whi Kim ◽  
Sung Min Nam ◽  
Dae Young Yoo ◽  
Hyo Young Jung ◽  
Il Yong Kim ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Genetic Background ◽  
Granule Cells ◽  
Treadmill Exercise ◽  
Inbred Mouse ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mouse Strains ◽  
Neuroblast Differentiation ◽  
Outbred Mouse

The genetic background of mice has various influences on the efficacy of physical exercise, as well as adult neurogenesis in the hippocampus. In this study, we investigated the basal level of hippocampal neurogenesis, as well as the effects of treadmill exercise on adult hippocampal neurogenesis in 9 mouse strains: 8 very commonly used laboratory inbred mouse strains (C57BL/6, BALB/c, A/J, C3H/HeJ, DBA/1, DBA/2, 129/SvJ, and FVB) and 1 outbred mouse strain (ICR). All 9 strains showed diverse basal levels of cell proliferation, neuroblast differentiation, and integration into granule cells in the sedentary group. C57BL/6 mice showed the highest levels of cell proliferation, neuroblast differentiation, and integration into granule cells at basal levels, and the DBA/2 mice showed the lowest levels. The efficacy of integration into granule cells was maximal in ICR mice. Treadmill exercise increased adult hippocampal neurogenesis in all 9 mouse strains. These results suggest that the genetic background of mice affects hippocampal neurogenesis and C57BL/6 mice are the most useful strain to assess basal levels of cell proliferation and neuroblast differentiation, but not maturation into granule cells. In addition, the DBA/2 strain is not suitable for studying hippocampal neurogenesis.

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