scholarly journals Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sebastian B. Arredondo ◽  
Daniel T. Reyes ◽  
Andrea Herrera-Soto ◽  
Muriel D. Mardones ◽  
Nibaldo C. Inestrosa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spatial Memory ◽  
Memory Task ◽  
Hippocampal Neurogenesis ◽  
Brdu Incorporation ◽  
Morphological Development ◽  
Cognitive Effect ◽  
Cognitive Improvement ◽  
Model Of Alzheimer’S Disease ◽  
Immature Neurons

AbstractIn Alzheimer´s disease (AD) there is a reduction in hippocampal neurogenesis that has been associated to cognitive deficits. Previously we showed that Andrographolide (ANDRO), the main bioactive component of Andrographis paniculate, induces proliferation in the hippocampus of the APPswe/PSEN1ΔE9 (APP/PS1) mouse model of AD as assessed by staining with the mitotic marker Ki67. Here, we further characterized the effect of ANDRO on hippocampal neurogenesis in APP/PS1 mice and evaluated the contribution of this process to the cognitive effect of ANDRO. Treatment of 8-month-old APP/PS1 mice with ANDRO for 4 weeks increased proliferation in the dentate gyrus as evaluated by BrdU incorporation. Although ANDRO had no effect on neuronal differentiation of newborn cells, it strongly increased neural progenitors, neuroblasts and newborn immature neurons, cell populations that were decreased in APP/PS1 mice compared to age-matched wild-type mice. ANDRO had no effect on migration or in total dendritic length, arborization and orientation of immature neurons, suggesting no effects on early morphological development of newborn neurons. Finally, ANDRO treatment improved the performance of APP/PS1 mice in the object location memory task. This effect was not completely prevented by co-treatment with the anti-mitotic drug TMZ, suggesting that other effects of ANDRO in addition to the increase in neurogenesis might underlie the observed cognitive improvement. Altogether, our data indicate that in APP/PS1 mice ANDRO stimulates neurogenesis in the hippocampus by inducing proliferation of neural precursor cells and improves spatial memory performance.

scholarly journals The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis

2020 ◽  
Vol 29 (12) ◽  
pp. 1950-1968
Author(s):  
Charlotte Castillon ◽  
Laurine Gonzalez ◽  
Florence Domenichini ◽  
Sandrine Guyon ◽  
Kevin Da Silva ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Spatial Memory ◽  
Adult Neurogenesis ◽  
Hippocampal Neurons ◽  
Memory Task ◽  
Clinical Signs ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Adult Born Neurons

Abstract The link between mutations associated with intellectual disability (ID) and the mechanisms underlying cognitive dysfunctions remains largely unknown. Here, we focused on PAK3, a serine/threonine kinase whose gene mutations cause X-linked ID. We generated a new mutant mouse model bearing the missense R67C mutation of the Pak3 gene (Pak3-R67C), known to cause moderate to severe ID in humans without other clinical signs and investigated hippocampal-dependent memory and adult hippocampal neurogenesis. Adult male Pak3-R67C mice exhibited selective impairments in long-term spatial memory and pattern separation function, suggestive of altered hippocampal neurogenesis. A delayed non-matching to place paradigm testing memory flexibility and proactive interference, reported here as being adult neurogenesis-dependent, revealed a hypersensitivity to high interference in Pak3-R67C mice. Analyzing adult hippocampal neurogenesis in Pak3-R67C mice reveals no alteration in the first steps of adult neurogenesis, but an accelerated death of a population of adult-born neurons during the critical period of 18–28 days after their birth. We then investigated the recruitment of hippocampal adult-born neurons after spatial memory recall. Post-recall activation of mature dentate granule cells in Pak3-R67C mice was unaffected, but a complete failure of activation of young DCX + newborn neurons was found, suggesting they were not recruited during the memory task. Decreased expression of the KCC2b chloride cotransporter and altered dendritic development indicate that young adult-born neurons are not fully functional in Pak3-R67C mice. We suggest that these defects in the dynamics and learning-associated recruitment of newborn hippocampal neurons may contribute to the selective cognitive deficits observed in this mouse model of ID.

Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer’s Disease

2015 ◽  
Vol 12 (9) ◽  
pp. 860-869 ◽  
Author(s):  
Yu Zhang ◽  
Furong Wang ◽  
Xianwen Luo ◽  
Li Wang ◽  
Peng Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Photic Stimulation ◽  
Cognitive Improvement ◽  
Model Of Alzheimer’S Disease

Effect of Soluble Amyloid Precursor Protein-alpha on Adult Hippocampal Neurogenesis in a Mouse Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
Shane M. Ohline ◽  
Connie Chan ◽  
Lucia Schoderboeck ◽  
Hollie E. Wicky ◽  
Warren P. Tate ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Hippocampal Neurogenesis ◽  
Precursor Protein ◽  
Adult Hippocampal Neurogenesis ◽  
Wild Type ◽  
Viral Expression ◽  
Model Of Alzheimer’S Disease

Abstract Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse model of Alzheimer’s disease. An adeno-associated virus-9 (AAV9) encoding murine sAPPα was injected into the hippocampus of 8 month-old wild-type and APP/PS1 mice, and later two different thymidine analogues (XdU) were systemically injected to label adult-born cells at different time points after viral transduction. The proliferation of adult-born cells, cell survival after eight weeks, and cell differentiation into either neurons or astrocytes was studied. Proliferation was impaired in APP/PS1 mice but was restored to wild-type levels by viral expression of sAPPα. In contrast, sAPPα overexpression failed to rescue the survival of XdU+-labelled cells that was impaired in APP/PS1 mice, although it did cause a significant increase in the area density of astrocytes in the granule cell layer across both genotypes. Finally, viral expression of sAPPα reduced amyloid-beta plaque load in APP/PS1 mice in the dentate gyrus and somatosensory cortex. These data add further evidence that increased levels of sAPPα could be therapeutic for the cognitive decline in AD, in part through restoration of the proliferation of neural progenitor cells in adults.

scholarly journals Physical Activity Ameliorates Impaired Hippocampal Neurogenesis in the Tg4-42 Mouse Model of Alzheimer’s Disease

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141989269 ◽  
Author(s):  
Anna-Lina Gerberding ◽  
Silvia Zampar ◽  
Martina Stazi ◽  
David Liebetanz ◽  
Oliver Wirths
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dentate Gyrus ◽  
Structural Changes ◽  
Hippocampal Neurogenesis ◽  
Wild Type ◽  
Running Wheel ◽  
Model Of Alzheimer’S Disease

There is growing evidence from epidemiological studies that especially midlife physical activity might exert a positive influence on the risk and progression of Alzheimer’s disease. In this study, the Tg4-42 mouse model of Alzheimer’s disease has been utilized to assess the effect of different housing conditions on structural changes in the hippocampus. Focusing on the dentate gyrus, we demonstrate that 6-month-old Tg4-42 mice have a reduced number of newborn neurons in comparison to age-matched wild-type mice. Housing these mice for 4 months with either unlimited or intermittent access to a running wheel resulted in a significant rescue of dentate gyrus neurogenesis. Although neither dentate gyrus volume nor neuron number could be modified in this Alzheimer’s disease mouse model, unrestricted access to a running wheel significantly increased dentate gyrus volume and granule cell number in wild-type mice.

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