Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer’s Disease

Article type: Research Article

Authors: Petukhova, Elena O.^a | Mukhamedshina, Yana O.^{a; b} | Salafutdinov, Ilnur I.^{a; b} | Garanina, Ekaterina E.^b | Kaligin, Maxim S.^b | Leushina, Alina V.^a | Rizvanov, Albert A.^b | Reis, Helton J.^c | Palotás, András^{b; d; *} | Zefirov, Andrey L.^a | Mukhamedyarov, Marat A.^{a; *}

Affiliations: [a] Kazan State Medical University, Kazan, Russia | [b] Kazan Federal University, Kazan, Russia | [c] Universidade Federal de Minas Gerais, Belo Horizonte, Brazil | [d] Asklepios-Med, Szeged, Hungary

Correspondence: [*] Correspondence to: Prof. Dr. Marat Mukhamedyarov and prof. Dr. András Palotás, Kazan State Medical University, Kazan, E-mail: [email protected] and [email protected].

Abstract: Background/Objective:Alzheimer’s disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues. Methods:UCBMCs were transduced with adenoviral vectors expressing GDNF and injected into AD transgenic mice. Various parameters including homing and survival of transplanted cells, expression of GDNF and synaptic proteins, as well as spatial memory were evaluated. Results:UCBMCs were observed in the hippocampus and cortex several weeks after transplantation, and their long-term presence was associated with improved spatial memory. Post-synaptic density protein 95 (PSD-95) and synaptophysin levels in the hippocampus were also effectively restored following the procedure in AD mice. Conclusions:Our data indicate that gene-cell therapy with GDNF-overexpressing UCBMCs may produce long-lasting neuroprotection and stimulation of synaptogenesis. Such adenoviral constructs could potentially possess a high therapeutic potential for the treatment of AD.

Keywords: Alzheimer’s disease, glial cell line-derived neuro-trophic factor, post-synaptic density protein 95, synaptophysin, umbilical cord blood mono-nuclear cells

DOI: 10.3233/JAD-190150

Journal: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 443-453, 2019