Application of neurotrophic factor-secreting cells (astrocyte - Like cells) in the in-vitro Alzheimer’s disease-like pathology on the human neuroblastoma cells

Jahed, Fatemeh Jafari; Rahbarghazi‬, Reza; Shafaei, Hajar; Rezabakhsh, Aysa; Karimipour, Mohammad

doi:10.1016/j.brainresbull.2021.04.014

Cited by 11 publications

(8 citation statements)

References 67 publications

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“…Our results showed that ADMSCs differentiated and exhibited classic astrocyte phenotype and could express the astrocyte marker GFAP in the cytoplasm. Further, the data of the present study displayed that NTFs secreting astrocyte-like cells increased the production of NGF and BDNF proteins [ 25 , 26 ] which are the two abundant members of the neurotrophin family in the hippocampus and cortex. They contribute to survival, synaptic plasticity, regenerative processes, and other various cellular functions via activating tyrosine receptors (Trk) [ 55 – 58 ].…”

Section: Discussionmentioning

confidence: 83%

“…Since the neurotrophic factors delivery can facilitate the bioactivity of neurons even in pathogenic conditions, stem cells as a vector for continuous NTFs delivery could be actual therapy for neurodegenerative disorders [ 50 – 52 ]. As previously demonstrated by Jahed et al NTF-SCs can reduce the AD pathology through down-regulation of hyperphosphorylated Tau protein and up-regulation of synaptophysin in in vitro conditions [ 26 ]. Further, the alleviation of neurodegenerative symptoms after transplantation of NTF-SCs has been revealed in other animal models.…”

Section: Discussionmentioning

confidence: 94%

“…The discovery of different stem cell types has revolutionized human medicine and is touted as an alternative approach to cure several pathologies. Among several types of stem cells, adipose tissue-derived stem cells can be differentiated into neurotrophic factor-secreting cells (NTF-SCs) with the ability to produce and secret neurotrophic factors like BDNF and NGF [ 25 , 26 ]. These cells have the advantage of transplantation and, as a vehicle that can deliver NTFs to the transplanted area further, have migratory ability to the injured regions [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…These cells have the advantage of transplantation and, as a vehicle that can deliver NTFs to the transplanted area further, have migratory ability to the injured regions [ 27 ]. The NTF-SCs have shown to be a valuable treatment in the AD in vitro model [ 26 ]. Since altered neurogenesis is a manifestation of AD, the therapy with the potency of neurogenesis enhancement seems favorable.…”

Section: Introductionmentioning

confidence: 99%

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Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice

et al. 2022

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Background Impairment in neurogenesis correlates with memory and cognitive dysfunction in AD patients. In the recent decade, therapies with stem cell bases are growing and proved to be efficient. This study is a preliminary attempt to explore the impact of NTF-SCs on hippocampal neurogenesis mediated by the Wnt/β-catenin signaling cascade in AD-like mouse brain parenchyma. Methods The BALB/c mice were divided into four groups: Control, AD +Vehicle, AD+ TF-SCs-CM and AD+NTF-SCs (n = 10). For AD induction, 100 µM Aβ1-42 was injected into lateral ventricles. The AD-like model was confirmed via passive avoidance test and Thioflavin-S staining 21 days following Aβ injection. Next, NTF-SCs were differentiated from ADMSCs, and both NTF-SCs and supernatant (NTF-SCs-CM) were injected into the hippocampus after AD confirmation. Endogenous neural stem cells (NSCs) proliferation capacity was assessed after 50 mg/kbW BrdU injection for 4 days using immunofluorescence (IF) staining. The percent of BrdU/Nestin and BrdU/NeuN positive NSCs were calculated. Real-time RT-PCR was used to detect genes related to the Wnt/β-catenin signaling cascade. The spatial learning and memory alternation was evaluated using the Morris water maze (MWM). Results Data showed the reduction in escape latency over 5 days in the AD mice compared to the control group. The administration of NTF-SCs and NTF-SCs-CM increased this value compared to the AD-Vehicle group. Both NTF-SCs and NTF-SCs-CM were the potential to reduce the cumulative distance to the platform in AD mice compared to the AD-Vehicle group. The time spent in target quadrants was ameliorated following NTF-SCs and NTF-SCs-CM transplantation followed by an improved MWM performance. IF imaging revealed the increase in BrdU/Nestin+ and BrdU/NeuN+ in AD mice that received NTF-SCs and NTF-SCs-CM, indicating enhanced neurogenesis. Based on real-time PCR analysis, the expression of PI3K, Akt, MAPK, ERK, Wnt, and β-catenin was upregulated and coincided with the suppression of GSK-3β after injection of NTF-SCs-CM and NTF-SCs. In this study, NTF-SCs had superior effects in AD mice that received NTF-SCs compared to NTF-SCs-CM. Conclusions The activation of Wnt/β-catenin pathway via NTF-SCs can be touted as a possible therapeutic approach to restore neurogenesis in AD mice.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice

et al. 2022

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“…In addition, the elevated expression level of HDAC4 was confirmed in the brain of AD patients and in mouse models. Indeed, the oral administration of Taq increases the levels of Syn2 and Homer1, which are upregulated in wide mice compared to 3xTg-AD mice [ 61 – 64 ] ( Figure 4 ).…”

Section: Hdac4 Promotes Age-related Diseasesmentioning

confidence: 99%

HDAC4 Inhibitors as Antivascular Senescence Therapeutics

Huang

Lin

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Aging is an inevitable consequence of life, and during this process, the epigenetic landscape changes and reactive oxygen species (ROS) accumulation increases. Inevitably, these changes are common in many age-related diseases, including neurodegeneration, hypertension, and cardiovascular diseases. In the current research, histone deacetylation 4 (HDAC4) was studied as a potential therapeutic target in vascular senescence. HDAC4 is a specific class II histone deacetylation protein that participates in epigenetic modifications and deacetylation of heat shock proteins and various transcription factors. There is increasing evidence to support that HDAC4 is a potential therapeutic target, and developments in the synthesis and testing of HDAC4 inhibitors are now gaining interest from academia and the pharmaceutical industry.

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Magnolol upregulates CHRM1 to attenuate Amyloid-β-triggered neuronal injury through regulating the cAMP/PKA/CREB pathway

et al. 2021

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Application of neurotrophic factor-secreting cells (astrocyte - Like cells) in the in-vitro Alzheimer’s disease-like pathology on the human neuroblastoma cells

Cited by 11 publications

References 67 publications

Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice

Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice

HDAC4 Inhibitors as Antivascular Senescence Therapeutics

Magnolol upregulates CHRM1 to attenuate Amyloid-β-triggered neuronal injury through regulating the cAMP/PKA/CREB pathway

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