IGF1 Gene Therapy Modifies Microglia in the Striatum of Senile Rats.

Eugenia Falomir-Lockhart,Luis Miguel García-Segura,Franco Juan Cruz Dolcetti,Claudia Beatriz Hereñú,Maria Jose Bellini

doi:10.3389/fnagi.2019.00048

Abstract

Microglial cells become dystrophic with aging; this phenotypic alteration contributes to basal central nervous system (CNS) neuroinflammation being a risk factor for age related neurodegenerative diseases. In previous studies we have observed that insulin like growth factor 1 (IGF1) gene therapy is a feasible approach to target brain cells, and that is effective to modify inflammatory response in vitro and to ameliorate cognitive or motor deficits in vivo. Based on these findings, the main aim of the present study is to investigate the effect of IGF1 gene therapy on microglia distribution and morphology in the senile rat. We found that IGF1 therapy leads to a region-specific modification of aged microglia population.

Highlights

Microglia, the immune cells of the central nervous system (CNS), suffer a phenotypic alteration during aging that is characterized by decreased motility and inefficient surveillance (Streit et al, 2004; von Bernhardi et al, 2016; Koellhoffer et al, 2017)
There was a higher number of Iba-1 immunoreactive cells in the animals injected with recombinant adenoviral vectors (RAd)-insulin like growth factor 1 (IGF1) than in the animals injected with RAd-Discosoma Red fluorescent protein (DsRed) (Figure 1)
No significant differences were detected in the number of Iba-1 immunoreactive cells in the motor cortex, substantia nigra and the perirhinal cortex (PRh) of the animals injected with RAd-IGF1 and the animals injected with RAd-DsRed (Figure 1)

Summary

Introduction

The immune cells of the central nervous system (CNS), suffer a phenotypic alteration during aging that is characterized by decreased motility and inefficient surveillance (Streit et al, 2004; von Bernhardi et al, 2016; Koellhoffer et al, 2017). A feasible approach to modulate microglia function in the aged brain is the use of neurotrophic factors that polarize these cells into a more neurotrophic/neuroprotective phenotype. In the present study we report that IGF1 therapy lead to a region-specific modification in microglia number and morphology in the aged brain

Objectives

Methods

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Conclusion