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


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Article Info

DATE

2022-07-26

AUTHORS

Gozal Bahlakeh, Reza Rahbarghazi, Ali Abedelahi, Saeed Sadigh-Eteghad, Mohammad Karimipour

ABSTRACT

BackgroundImpairment 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.MethodsThe 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).ResultsData 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.ConclusionsThe activation of Wnt/β-catenin pathway via NTF-SCs can be touted as a possible therapeutic approach to restore neurogenesis in AD mice. More... »

PAGES

343

References to SciGraph publications

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    http://scigraph.springernature.com/pub.10.1186/s13287-022-03024-6

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    33 schema:description BackgroundImpairment 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.MethodsThe 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).ResultsData 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.ConclusionsThe 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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    40 AD induction
    41 AD mice
    42 AD model mice
    43 AD patients
    44 AD-like model
    45 ADMSCs
    46 Akt
    47 Aβ injection
    48 Aβ1-42
    49 BALB/c mice
    50 BackgroundImpairment
    51 BrdU injection
    52 BrdU/
    53 BrdU/nestin
    54 CM
    55 CM transplantation
    56 ConclusionsThe activation
    57 ERK
    58 GSK-3β
    59 MAPK
    60 MWM performance
    61 Morris water maze
    62 NSCs
    63 PCR analysis
    64 PI3K
    65 RT-PCR
    66 ResultsData
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    68 Wnt
    69 Wnt/β-catenin
    70 Wnt/β-catenin pathway
    71 activation
    72 administration
    73 alternation
    74 analysis
    75 approach
    76 attempt
    77 avoidance test
    78 basis
    79 brain parenchyma
    80 c mice
    81 capacity
    82 cascade
    83 cell basis
    84 cell proliferation capacity
    85 cells
    86 cognitive dysfunction
    87 confirmation
    88 control
    89 control group
    90 cumulative distance
    91 days
    92 decades
    93 distance
    94 dysfunction
    95 effect
    96 endogenous hippocampal neurogenesis
    97 enhanced neurogenesis
    98 escape latency
    99 expression
    100 genes
    101 group
    102 hippocampal neurogenesis
    103 hippocampus
    104 imaging
    105 immunofluorescence staining
    106 impact
    107 increase
    108 induction
    109 injection
    110 latency
    111 lateral ventricle
    112 learning
    113 maze
    114 memory
    115 mice
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    120 neurogenesis
    121 neurotrophic factor-secreting cells
    122 parenchyma
    123 passive avoidance test
    124 pathway
    125 patients
    126 percent
    127 performance
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    129 possible therapeutic approaches
    130 potential
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    133 quadrant
    134 real-time PCR analysis
    135 real-time RT-PCR
    136 recent decades
    137 reduction
    138 spatial learning
    139 staining
    140 stem cell basis
    141 study
    142 superior effect
    143 supernatant
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    145 target quadrant
    146 test
    147 therapeutic approaches
    148 therapy
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    150 time
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