scholarly journals Implication of Adult Hippocampal Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 286
Author(s):  
Hesham Essa ◽  
Lee Peyton ◽  
Whidul Hasan ◽  
Brandon Emanuel León ◽  
Doo-Sup Choi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Neurofibrillary Tangles ◽  
Neuronal Loss ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Key Factors ◽  
App Gene

Alzheimer’s disease is the most common neurodegenerative disease, affecting more than 6 million US citizens and representing the most prevalent cause for dementia. Neurogenesis has been repeatedly reported to be impaired in AD mouse models, but the reason for this impairment remains unclear. Several key factors play a crucial role in AD including Aβ accumulation, intracellular neurofibrillary tangles accumulation, and neuronal loss (specifically in the dentate gyrus of the hippocampus). Neurofibrillary tangles have been long associated with the neuronal loss in the dentate gyrus. Of note, Aβ accumulation plays an important role in the impairment of neurogenesis, but recent studies started to shed a light on the role of APP gene expression on the neurogenesis process. In this review, we will discuss the recent approaches to neurogenesis in Alzheimer disease and update the development of therapeutic methods.

scholarly journals Adult Hippocampal Neurogenesis in Aging and Alzheimer's Disease

2021 ◽  
Vol 16 (4) ◽  
pp. 681-693 ◽  
Author(s):  
Kelsey R. Babcock ◽  
John S. Page ◽  
Justin R. Fallon ◽  
Ashley E. Webb
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Does Impairment of Adult Neurogenesis Contribute to Pathophysiology of Alzheimer's Disease? A Still Open Question

2021 ◽  
Vol 13 ◽  
Author(s):  
Domenica Donatella Li Puma ◽  
Roberto Piacentini ◽  
Claudio Grassi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Adult Neurogenesis ◽  
Memory Formation ◽  
Hippocampal Neurogenesis ◽  
Synaptic Function ◽  
Adult Hippocampal Neurogenesis ◽  
Amyloid Β Protein

Adult hippocampal neurogenesis is a physiological mechanism contributing to hippocampal memory formation. Several studies associated altered hippocampal neurogenesis with aging and Alzheimer's disease (AD). However, whether amyloid-β protein (Aβ)/tau accumulation impairs adult hippocampal neurogenesis and, consequently, the hippocampal circuitry, involved in memory formation, or altered neurogenesis is an epiphenomenon of AD neuropathology contributing negligibly to the AD phenotype, is, especially in humans, still debated. The detrimental effects of Aβ/tau on synaptic function and neuronal viability have been clearly addressed both in in vitro and in vivo experimental models. Until some years ago, studies carried out on in vitro models investigating the action of Aβ/tau on proliferation and differentiation of hippocampal neural stem cells led to contrasting results, mainly due to discrepancies arising from different experimental conditions (e.g., different cellular/animal models, different Aβ and/or tau isoforms, concentrations, and/or aggregation profiles). To date, studies investigating in situ adult hippocampal neurogenesis indicate severe impairment in most of transgenic AD mice; this impairment precedes by several months cognitive dysfunction. Using experimental tools, which only became available in the last few years, research in humans indicated that hippocampal neurogenesis is altered in cognitive declined individuals affected by either mild cognitive impairment or AD as well as in normal cognitive elderly with a significant inverse relationship between the number of newly formed neurons and cognitive impairment. However, despite that such information is available, the question whether impaired neurogenesis contributes to AD pathogenesis or is a mere consequence of Aβ/pTau accumulation is not definitively answered. Herein, we attempted to shed light on this complex and very intriguing topic by reviewing relevant literature on impairment of adult neurogenesis in mouse models of AD and in AD patients analyzing the temporal relationship between the occurrence of altered neurogenesis and the appearance of AD hallmarks and cognitive dysfunctions.

scholarly journals Chronic Memantine Treatment Ameliorates Behavioral Deficits, Neuron Loss, and Impaired Neurogenesis in a Model of Alzheimer’s Disease

2020 ◽  
Vol 58 (1) ◽  
pp. 204-216
Author(s):  
Martina Stazi ◽  
Oliver Wirths
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Recognition Task ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Behavioral Deficits ◽  
Neuron Loss ◽  
Beneficial Effects ◽  
Memantine Treatment

AbstractMemantine, a non-competitive NMDA receptor antagonist possessing neuroprotective properties, belongs to the small group of drugs which have been approved for the treatment of Alzheimer’s disease (AD). While several preclinical studies employing different transgenic AD mouse models have described beneficial effects with regard to rescued behavioral deficits or reduced amyloid plaque pathology, it is largely unknown whether memantine might have beneficial effects on neurodegeneration. In the current study, we assessed whether memantine treatment has an impact on hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD. We demonstrate that a chronic oral memantine treatment for 4 months diminishes hippocampal CA1 neuron loss and rescues learning and memory performance in different behavioral paradigms, such as Morris water maze or a novel object recognition task. Cognitive benefits of chronic memantine treatment were accompanied by an amelioration of impaired adult hippocampal neurogenesis. Taken together, our results demonstrate that memantine successfully counteracts pathological alterations in a preclinical mouse model of AD.

scholarly journals The Effects of Gene-Environment Interactions Between Cadmium Exposure and Apolipoprotein E4 on Memory in a Mouse Model of Alzheimer’s Disease

2019 ◽  
Author(s):  
Liang Zhang ◽  
Hao Wang ◽  
Glen M Abel ◽  
Daniel R Storm ◽  
Zhengui Xia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Health Concern ◽  
Apoe Ε4 ◽  
Gene Environment ◽  
Cd Exposure

Abstract Cadmium (Cd) is a heavy metal of great public health concern. Recent studies suggested a link between Cd exposure and cognitive decline in humans. The ε4 allele, compared with the common ε3 allele, of the human apolipoprotein E gene (ApoE) is associated with accelerated cognitive decline and increased risks for Alzheimer’s disease (AD). To investigate the gene-environment interactions (GxE) between ApoE-ε4 and Cd exposure on cognition, we used a mouse model of AD that expresses human ApoE-ε3 (ApoE3-KI [knock-in]) or ApoE-ε4 (ApoE4-KI). Mice were exposed to 0.6 mg/l CdCl2 through drinking water for 14 weeks and assessed for hippocampus-dependent memory. A separate cohort was sacrificed immediately after exposure and used for Cd measurements and immunostaining. The peak blood Cd was 0.3–0.4 µg/l, within levels found in the U.S. general population. All Cd-treated animals exhibited spatial working memory deficits in the novel object location test. This deficit manifested earlier in ApoE4-KI mice than in ApoE3-KI within the same sex and earlier in males than females within the same genotype. ApoE4-KI but not ApoE3-KI mice exhibited reduced spontaneous alternation later in life in the T-maze test. Finally, Cd exposure impaired neuronal differentiation of adult-born neurons in the hippocampus of male ApoE4-KI mice. These data suggest that a GxE between ApoE4 and Cd exposure leads to accelerated cognitive impairment and that impaired adult hippocampal neurogenesis may be one of the underlying mechanisms. Furthermore, male mice were more susceptible than female mice to this GxE effect when animals were young.

scholarly journals Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease

2019 ◽  
Vol 20 (12) ◽  
pp. 3030 ◽  
Author(s):  
Soo Jung Shin ◽  
Seong Gak Jeon ◽  
Jin-il Kim ◽  
Yu-on Jeong ◽  
Sujin Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Formation ◽  
Experimental Models ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Red Ginseng ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.

scholarly journals Relationship of Wine Consumption with Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 206 ◽  
Author(s):  
Reale ◽  
Costantini ◽  
Jagarlapoodi ◽  
Khan ◽  
Belwal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alcohol Intake ◽  
Senile Plaques ◽  
Neuronal Loss ◽  
Language Function ◽  
Reduce Risk ◽  
Relationship Of ◽  
The Relationship

Background: Alzheimer’s disease (AD), the most threatening neurodegenerative disease, is characterized by the loss of memory and language function, an unbalanced perception of space, and other cognitive and physical manifestations. The pathology of AD is characterized by neuronal loss and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in AD is being actively studied, and nutrition is one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest, with varying and often conflicting results. Scope and Approach: With this review, we aimed to critically summarize the main relevant studies to clarify the relationship between wine drinking and AD, as well as how frequency and/or amount of drinking may influence the effects. Key Findings and Conclusions: Overall, based on the interpretation of various studies, no definitive results highlight if light to moderate alcohol drinking is detrimental to cognition and dementia, or if alcohol intake could reduce risk of developing AD.

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