Effect of brain-derived neurotrophic factor modified human amniotic mesenchymal stem cell transplantation on cognitive function in Alzheimer’s disease rats

doi:10.12307/2022.331

Abstract

Abstract: BACKGROUND: Studies have found that human mesenchymal stem cells modified by brain-derived neurotrophic factor (BDNF) can be used to treat spinal cord injury and traumatic brain injury, but whether there is a curative effect on Alzheimer’s disease is rare in the past reports.
OBJECTIVE: To observe the effects of BDNF modified human amniotic mesenchymal stem cells (hAMSCs) on learning and memory ability and expression of choline acetyltransferase in hippocampus and nerve growth factor in basal forebrain of rats with Alzheimer’s disease.
METHODS: Forty healthy male adult SD rats were randomly divided into control group, model group, hAMSCs group and BDNF-hAMSCs group with 10 rats in each group. Bilateral hippocampal injection of β-amyloid 25-35 was used to construct an Alzheimer’s disease model. On day 14, 10 μL of hAMSCs or 10 μL of BDNF were injected into the posterior ventricle to transfect hAMSCs. At 2 weeks after transplantation, learning and memory abilities of rats were evaluated by Morris water maze test. Choline acetyltransferase expression in hippocampus was detected by immunohistochemistry. Nerve growth factor expression in the basal forebrain was detected by RT-PCR.
RESULTS AND CONCLUSION: (1) At 3, 4, and 5 days of Morris water maze test, the escape latencies of the hAMSCs group and the BDNF-hAMSCs group were lower than that in the model group (P < 0.05). At 4 and 5 days, the escape latency of the BDNF-hAMSCs group was lower than that of the hAMSCs group (P < 0.05). (2) The number of choline acetyltransferase positive neurons and nerve growth factor expression in the basal forebrain in hippocampus of model group were significantly lower than those of control group (P < 0.05). The number of choline acetyltransferase positive neurons in the hippocampus and nerve growth factor expression in the basal forebrain of the hAMSCs group and the BDNF-hAMSCs group were higher than those of the model group (P < 0.05), and the number of choline acetyltransferase positive neurons and nerve growth factor expression in the BDNF-hAMSCs group were higher than those in the hAMSCs group (P < 0.05). (3) Results suggest that modification of hAMSCs with BDNF can further improve the efficacy of stem cells in the treatment of Alzheimer’s disease, and can significantly increase the expression levels of choline acetyltransferase in the hippocampus and nerve growth factor in the basal forebrain.

Key words: stem cells, human amniotic mesenchymal stem cells, brain-derived neurotrophic factor, alzheimer’s disease, choline acetyltransferase, brain nerve growth factor, cognitive function

CLC Number:

Wang Yuxiang, Cui Chuanju, Li Yanling, Li Aifan. Effect of brain-derived neurotrophic factor modified human amniotic mesenchymal stem cell transplantation on cognitive function in Alzheimer’s disease rats[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(13): 2045-2049.

Figures/Tables 7

References

[1] HORVATH A, SZUCS A, CSUKLY G, et al. EEG and ERP biomarkers of Alzheimer’s disease: a critical review. Front Biosci (Landmark Ed). 2018;23:183-220.
[2] CHEN YG. Research Progress in the Pathogenesis of Alzheimer’s Disease. Chin Med J (Engl). 2018;131(13):1618-1624.
[3] MARESOVA P, TOMSONE S, LAMESKI P, et al. Technological Solutions for Older People with Alzheimer’s Disease: Review. Curr Alzheimer Res. 2018;15(10):975-983.
[4] ROSS CA, AKIMOV SS. Human-induced pluripotent stem cells: potential for neurodegenerative diseases. Hum Mol Genet. 2014;23(R1):R17-26.
[5] JIANG Y, FAY JM, POON CD, et al. Nanoformulation of Brain-Derived Neurotrophic Factor with Target Receptor-Triggered-Release in the Central Nervous System. Adv Funct Mater. 2018;28(6):1703982.
[6] YÜCEL F, YAMAN SO, OZBABALIK D, et al. Morphometric measurements of MRI findings in patients with Alzheimer’s disease. Adv Clin Exp Med. 2014;23(1):91-96.
[7] IULITA MF, BISTUÉ MILLÓN MB, PENTZ R, et al. Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer’s disease. Neurobiol Dis. 2017;108:307-323.
[8] LI LM, HUANG LL, JIANG XC, et al. Transplantation of BDNF Gene Recombinant Mesenchymal Stem Cells and Adhesive Peptide-modified Hydrogel Scaffold for Spinal Cord Repair. Curr Gene Ther. 2018;18(1): 29-39.
[9] HEI WH, ALMANSOORI AA, SUNG MA, et al. Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor (BDNF) tohuman umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) promotescrush-injured rat sciatic nerve regeneration. Neurosci Lett. 2017;643:111-120.
[10] WANG Z, XU P, CHEN B, et al. Identifying circRNA-associated-ceRNA networks in the hippocampus of Aβ1-42-induced Alzheimer’s disease-like rats using microarray analysis. Aging (Albany NY). 2018;10(4): 775-788.
[11] WANG Y, HAN S, HAN R, et al. Propofol-induced downregulation of NR2B membrane translocation in hippocampus and spatial memory deficits of neonatal mice. Brain Behav. 2017;7(7):e00734.
[12] CHEN X, XIAO JW, CAO P, et al. Brain-derived neurotrophic factor protects against acrylamide-induced neuronal and synaptic injury via the TrkB-MAPK-Erk1/2 pathway. Neural Regen Res. 2021;16(1):150-157.
[13] AHMED S, REYNOLDS BA, WEISS S. BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors. J Neurosci. 1995;15(8):5765-5778.
[14] MA H, YU B, KONG L, et al. Neural stem cells over-expressing brain-derived neurotrophic factor (BDNF) stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury. Neurochem Res. 2012;37(1):69-83.
[15] YANG JW, MA W, LUO T, et al. BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway. Growth Factors. 2016;34(1-2):19-32.
[15] ROSENBLUM S, SMITH TN, WANG N, et al. BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery After Transplantation in Hypoxic-Ischemic Stroke. Cell Transplant. 2015;24(12):2449-2461.
[17] MARSH SE, BLURTON-JONES M. Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support. Neurochem Int. 2017;106:94-100.
[18] WU CC, LIEN CC, HOU WH, et al. Gain of BDNF Function in Engrafted Neural Stem Cells Promotes the Therapeutic Potential for Alzheimer’s Disease. Sci Rep. 2016;6:27358.
[19] RUAN Q, YU Z, ZHANG W, et al. Cholinergic Hypofunction in Presbycusis-Related Tinnitus With Cognitive Function Impairment: Emerging Hypotheses. Front Aging Neurosci. 2018;10:98.
[20] JAMAL M, ITO A, TANAKA N, et al. The Role of Apolipoprotein E and Ethanol Exposure in Age-Related Changes in Choline Acetyltransferase and Brain-Derived Neurotrophic Factor Expression in the Mouse Hippocampus. J Mol Neurosci. 2018;65(1):84-92.
[21] RAFII MS, TUSZYNSKI MH, THOMAS RG, et al. Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2018;75(7):834-841.