Neurogenesis in aging and age-related neurodegenerative diseases

Čulig, Luka; Chu, Xixia; Bohr, Vilhelm A.

doi:10.1016/j.arr.2022.101636

Cited by 91 publications

(43 citation statements)

References 525 publications

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“…Many studies have confirmed that adult neurogenesis in aged rodents is approximately 3–9 times lower compared to juveniles. The age-related deterioration of adult neurogenesis includes every stage of this process: the proliferation, differentiation, maturation and survival of newly formed neurons [ 8 , 69 , 70 , 71 ]. Age-related decline in adult human neurogenesis remains controversial [ 72 ], although Moreno-Jiménez et al [ 12 ] showed a negative correlation between the number of immature neurons and age in healthy people.…”

Section: Discussionmentioning

confidence: 99%

“…Newly generated neurons are incorporated into existing neural circuits of the hippocampus (in the DG and hippocampal subregions CA1–CA3) and play an important role in hippocampus-dependent learning and memory (e.g., spatial navigation, spatial memory and orientation). Moreover, adult hippocampal neurogenesis ensures and maintains the functional integrity of this structure, especially in aged individuals, which allows for the formation of new memories, thereby increasing the efficiency of contextual memory, and facilitates learning [ 6 , 8 ]. By contrast, new neurons in the OB play a critical role in perception and memory processes related to odours, which in adults may be associated with behavioural adaptive mechanisms in response to environmental changes.…”

Section: Introductionmentioning

confidence: 99%

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Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats

Kurowska

Ruciński

Myślińska

et al. 2022

IJMS

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The disorder of adult neurogenesis is considered an important mechanism underlying the learning and memory impairment observed in Alzheimer’s disease (AD). The sporadic nonhereditary form of AD (sAD) affects over 95% of AD patients and is related to interactions between genetic and environmental factors. An intracerebroventricular injection of streptozotocin (STZ-ICV) is a representative and well-established method to induce sAD-like pathology. Dimethyl fumarate (DMF) has antioxidant and anti-inflammatory properties and is used for multiple sclerosis treatment. The present study determines whether a 26-day DMF therapy ameliorates the disruption of adult neurogenesis and BDNF-related neuroprotection in the hippocampus and olfactory bulb (OB) in an STZ-ICV rat model of sAD. Considering age as an important risk factor for developing AD, this study was performed using 3-month-old (the young group) and 22-month-old (the aged group) male Wistar rats. Spatial cognitive functions were evaluated with the Morris water maze task. Immunofluorescent labelling was used to assess the parameters of adult neurogenesis and BDNF-related neuroprotection in the hippocampus and OB. Our results showed that the STZ-ICV evoked spatial learning and memory impairment and disturbances in adult neurogenesis and BDNF expression in both examined brain structures. In the aged animals, the deficits were more severe. We found that the DMF treatment significantly alleviated STZ-ICV-induced behavioural and neuronal disorders in both age groups of the rats. Our findings suggest that DMF, due to its beneficial effect on the formation of new neurons and BDNF-related neuroprotection, may be considered as a promising new therapeutic agent in human sAD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats

Kurowska

Ruciński

Myślińska

et al. 2022

IJMS

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“…Adult neurogenesis is of great medical significance to cognitive, memory, and motor dysfunction caused by central nervous system diseases (Culig et al, 2022). Experimental evidence shows that intermittent hypobaric hypoxia can promote the proliferation of endogenous neural progenitor cells, leading to an increase in the number of new neurons, and produces antidepressant-like effects.…”

Section: Hypoxia and Neurovascular Regenerationmentioning

confidence: 99%

Intermittent hypoxia conditioning as a potential prevention and treatment strategy for ischemic stroke: Current evidence and future directions

Yuan

Liu

et al. 2022

Front. Neurosci.

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Ischemic stroke (IS) is the leading cause of disability and death worldwide. Owing to the aging population and unhealthy lifestyles, the incidence of cerebrovascular disease is high. Vascular risk factors include hypertension, diabetes, dyslipidemia, and obesity. Therefore, in addition to timely and effective reperfusion therapy for IS, it is crucial to actively control these risk factors to reduce the incidence and recurrence rates of IS. Evidence from human and animal studies suggests that moderate intermittent hypoxia (IH) exposure is a promising therapeutic strategy to ameliorate common vascular risk factors and comorbidities. Given the complex pathophysiological mechanisms underlying IS, effective treatment must focus on reducing injury in the acute phase and promoting repair in the recovery phase. Therefore, this review discusses the preclinical perspectives on IH conditioning as a potential treatment for neurovascular injury and highlights IH pre and postconditioning strategies for IS. Hypoxia conditioning reduces brain injury by increasing resistance to acute ischemic and hypoxic stress, exerting neuroprotective effects, and promoting post-injury repair and regeneration. However, whether IH produces beneficial effects depends not only on the hypoxic regimen but also on inter-subject differences. Therefore, we discuss the factors that may influence the effectiveness of IH treatment, including age, sex, comorbidities, and circadian rhythm, which can be used to help identify the optimal intervention population and treatment protocols for more accurate, individualized clinical translation. In conclusion, IH conditioning as a non-invasive, non-pharmacological, systemic, and multi-targeted intervention can not only reduce brain damage after stroke but can also be applied to the prevention and functional recovery of IS, providing brain protection at different stages of the disease. It represents a promising therapeutic strategy. For patients with IS and high-risk groups, IH conditioning is expected to develop as an adjunctive clinical treatment option to reduce the incidence, recurrence, disability, and mortality of IS and to reduce disease burden.

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“…Compared with adult neurogenesis in the SGZ, few studies have focused on adult neurogenesis in the SVZ, but it is evident that the alteration of adult SVZ neurogenesis plays a crucial role in AD ( Scopa et al, 2020 ; Culig et al, 2022 ). In addition, adult SVZ neurogenesis has been proposed in several studies as a promising therapeutic target for neurodegenerative diseases, including AD ( Mu and Gage, 2011 ; Culig et al, 2022 ). Furthermore, SVZ-derived newborn neurons could help compensate for the reduced the neuronal population and restore impaired neural circuits in AD ( Brinton and Wang, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Relationship between adult subventricular neurogenesis and Alzheimer’s disease: Pathologic roles and therapeutic implications

Kim

Shin

Kim

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by irreversible cognitive declines. Senile plaques formed by amyloid-β (Aβ) peptides and neurofibrillary tangles, consisting of hyperphosphorylated tau protein accumulation, are prominent neuropathological features of AD. Impairment of adult neurogenesis is also a well-known pathology in AD. Adult neurogenesis is the process by which neurons are generated from adult neural stem cells. It is closely related to various functions, including cognition, as it occurs throughout life for continuous repair and development of specific neural pathways. Notably, subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, transports neurons to several brain regions such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. These migrating neurons can affect cognitive function and behavior in different neurodegenerative diseases. Despite several studies indicating the importance of adult SVZ neurogenesis in neurodegenerative disorders, the pathological alterations and therapeutic implications of impaired adult neurogenesis in the SVZ in AD have not yet been fully explained. In this review, we summarize recent progress in understanding the alterations in adult SVZ neurogenesis in AD animal models and patients. Moreover, we discuss the potential therapeutic approaches for restoring impaired adult SVZ neurogenesis. Our goal is to impart to readers the importance of adult SVZ neurogenesis in AD and to provide new insights through the discussion of possible therapeutic approaches.

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Neurogenesis in aging and age-related neurodegenerative diseases

Cited by 91 publications

References 525 publications

Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats

Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats

Intermittent hypoxia conditioning as a potential prevention and treatment strategy for ischemic stroke: Current evidence and future directions

Relationship between adult subventricular neurogenesis and Alzheimer’s disease: Pathologic roles and therapeutic implications

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