Stimulation of neurogenesis at hippocampus in Alzheimer's disease


Cite item

Full Text

Abstract

Alzheimer's disease is a chronic neurodegenerative disease, which is characterized by specific pathomorphological changes in brain including hippocampus One of prospective direction in development of approaches for treatment of Alzheimer's disease is use of gene-cell technologies In present work we studied the possibility to stimulate neurogenesis at hippocampus of APP/PS1 transgenic mice by transplantation of umbilical cord blood mononuclear cells transduced with adenoviral vector overexpressing recombinant glial neurotrophic factor (GDNF). Effectiveness of therapy was evaluated basing on immunoexpression of stem and progenitor cells (using antibodies against doublecortin and nestin) in different hippocampal areas Analysis of obtained data showed that transplantation of umbilical cord blood mononuclear cells overexpressing glial neurotrophic factor or enhanced green fluorescent protein stimulates processes of neurogenesis at hippocampus of transgenic mice with Alzheimer's disease model, certifying high therapeutic potential of these gene-cell constructs

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

O. Y Vasilieva

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

L. Y Aksenova

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

V. V Solovyeva

Kazan (Volga Region) Federal University

E. E Garanina

Kazan (Volga Region) Federal University

A. A Rizvanov

Kazan (Volga Region) Federal University

A. L Zefirov

Kazan State Medical University

R. R Islamov

Kazan State Medical University

M. A Mukhamedyarov

Kazan State Medical University

Email: maratm80@list.ru

References

  1. Altman J., Bayer S.A. Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J. Comp. Neurol. 1990; 301: 365-81.
  2. Bedard A., Parent A. Evidence of newly generated neurons in the human olfactory bulb. Brain Res Dev Brain Res. 2004; 151: 159-68.
  3. Gould E., Reeves A.J., Graziano M.S. et al. Neurogenesis in the neocortex of adult primates. Science. 1999; 286: 548-52.
  4. Zhao C., Deng W., Gage F.H. Mechanisms and functional implications of adult neurogenesis. Cell 2008; 132: 645-60
  5. Schaeffer E.L., Novaes B.A., da Silva E.R. et al. Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain. Prog. Neuropsychopharmacol. Biol. Psychiatry 2009; 33: 1087-102.
  6. 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. 7; 7. 1.
  7. Черенкова Е.Е., Федотова В.Ю., Борисов М.А. и др. Создание рекомбинантных аденовирусов и лентивирусов, экспрессирующих ангиогенные и нейропротекторные факторы, с помощью технологии клонирования Gateway. клеточная трансплантология и тканевая инженерия 2012; 7(3): 164-8.
  8. Исламов Р.Р., Ризванов А.А., Черенкова Е.Е. и др. Исследование экспрессии рекомбинантных терапевтических генов в мононуклеарных клетках крови пуповины,трансдуцированных тремя аденовирусными векторами, кодирующими нейротрофические факторы GDNF и VEGF и молекулу нейрональной адгезии NCAM. Гены и клетки 2014; 9(3): 204-8.
  9. Iosif R. E., Ekdahl C. T., Ahlenius H. et al. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J. Neurosci. 2006; 26: 9703-12.
  10. Kotani S., Yamauchi T., Teramoto T. et al. Donepezil, an acetylcholinesterase inhibitor, enhances adult hippocampal neurogenesis. Chem. Biol. Interact. 2008; 175: 227-30.
  11. Richetin K., Leclerc C., Toni N. et al. Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease. Brain 2015; 138: 440-55.
  12. 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.
  13. 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
  14. 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.
  15. Петухова Е.О., Мухамедшина Я.О., Ризванов А.А. и др. Трансплантация мононуклеарных клеток пуповинной крови человека улучшает пространственную память у APP/PS1 трансгенных мышей с моделью болезни Альцгеймера. Гены и клетки 2014; 9: 40-5.

Copyright (c) 2015 PJSC Human Stem Cells Institute


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 - 57156 от 11.03.2014.

This website uses cookies

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

About Cookies