Transplantation of mononuclear cells of human umbilical cord blood improves spatial memory in APP/PS1 transgenic mice with alzheimer's disease model


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Alzheimer's disease is progressive incurable neurodegenerative disease, which is manifested mainly by dementia. One of the most promising directions in development of Alzheimer's disease treatment is use of gene-cell technologies. The aim of current study was to perform transplantation of wild-type or EGFP expressing umbilical cord blood mononuclear cells (МКПК) to APP/PS1 transgenic mice with Alzheimer's disease model with further evaluation of transplantation impact with behavioral (T-maze, plus maze, open field) and immunohistochemical methods. It was found that МКПК transplantation significantly ameliorates behavioral performance of APP/PS1 mice: improves spatial memory, decreases anxiety and non-specific excitability, increases the efficacy of exploratory behavior. Grafted cells were found in cortex and hippocampus of mice even 3 months after МКПК transplantation, herewith EGFP expression in grafted cells was found at early stages after transplantation. Thus, use of МКПК-based gene-cell constructs represents a promising direction in development of Alzheimer's disease therapy.

Full Text

Restricted Access

About the authors

E. O Petukhova

Kazan State Medical University

Y. O Mukhamedshina

Kazan State Medical University; Kazan (Volga region) Federal University

A. A Rizvanov

Kazan (Volga region) Federal University

A. R Mukhitov

Kazan Institute of biochemistry and biophysics of RAS

A. L Zefirov

Kazan State Medical University

R. R Islamov

Kazan State Medical University

M. A Mukhamedyarov

Kazan State Medical University

References

  1. Prince M., Bryce R., Albanese E. et al. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013; 9: 63-75 e62.
  2. Мухамедьяров М.А., Зефиров А.Л. Влияние р-амилоидного пептида на функции возбудимых тканей: физиологические и патологические аспекты. Успехи физиологических наук 2013; 44: 55-71.
  3. Querfurth H.W., LaFerla F.M. Alzheimer's disease. N. Engl. J. Med. 2010; 362: 329-44.
  4. Lu B., Nagappan G., Guan X. et al. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat. Rev. Neurosci. 2013; 14: 401-16.
  5. Sopova K., Gatsiou K., Stellos K. et al. Dysregulation of neurotrophic and haematopoietic growth factors in Alzheimer's disease: from pathophysiology to novel treatment strategies. Curr. Alzheimer Res. 2014; 11: 27-39.
  6. Tuszynski M.H. Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 2007; 21: 179-89.
  7. Ernfors P., Bramham C.R. The coupling of a trkB tyrosine residue to LTP. Trends Neurosci. 2003; 26: 171-3.
  8. Nagahara A.H., Merrill D.A., Coppola G. et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat. Med. 2009; 15: 331-7.
  9. Newman M.B., Willing A.E., Manresa J.J. et al. Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair. Exp. Neurol. 2006; 199: 201-8.
  10. Neuhoff S., Moers J., Rieks M. et al. Proliferation, differentiation, and cytokine secretion of human umbilical cord blood-derived mononuclear cells in vitro. Exp. Hematol. 2007; 35: 1119-31.
  11. Fan C.G., Zhang Q.J., Tang F.W. et al. Human umbilical cord blood cells express neurotrophic factors. Neurosci. Lett. 2005; 380: 322-5.
  12. Chen N., Newcomb J., Garbuzova-Davis S. et al. Human umbilical cord blood cells have trophic effects on young and aging hippocampal neurons in vitro. Aging Dis. 2010; 1: 173-90.
  13. Fuss I.J., Kanof M.E., Smith P.D. et al. Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr. Protoc. Immunol. 2009; Chapter 7: Unit7.1.
  14. Завалишин И.А., Бочков Н.П., Суетна З.А. и др. Генная терапия бокового амиотрофического склероза. Бюллетень экспериментальной биологии и медицины 2008; 145: 467-70.
  15. Deacon R.M., Rawlins J.N. T-maze alternation in the rodent. Nat. Protoc. 2006; 1: 7-12.
  16. Salimov R. M., McBride W. J., Sinclair J. D. et al. Performance in the cross-maze and slip funnel tests of four pairs of rat lines selectively bred for divergent alcohol drinking behavior. Addict. Biol. 1996; 1: 273-80.
  17. Markina N.V., Salimov R.M., Poletaeva I.I. Behavioral screening of two mouse lines selected for different brain weight. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2001; 25: 1083-9.
  18. Selkoe D.J. Alzheimer's disease is a synaptic failure. Science 2002; 298: 789-91.
  19. Garden G.A., La Spada A.R. Intercellular (mis)communication in neurodegenerative disease. Neuron 2012; 73: 886-901.
  20. Garbuzova-Davis S., Willing A.E., Zigova T. et al. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J. Hematother. Stem Cell Res. 2003; 12: 255-70.
  21. Rizvanov A.A., Guseva D.S., Salafutdinov I.I. et al. Genetically modified human umbilical cord blood cells expressing vascular endothelial growth factor and fibroblast growth factor 2 differentiate into glial cells after transplantation into amyotrophic lateral sclerosis transgenic mice. Exp. Biol. Med. (Maywood). 2010; 236(1): 91-8.
  22. Rizvanov A.A., Kiyasov A.P., Gaziziov I.M. et al. Human umbilical cord blood cells transfected with VEGF and L(1)CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis-a novel approach in stem cell therapy. Neurochem. Int. 2008; 53: 389-94.

Copyright (c) 2014 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies