Acta clinica Croatica, Vol. 62. No. 1, 2023.
Original scientific paper
https://doi.org/10.20471/acc.2023.62.01.21
Hippocampal Ganglioside Composition is Altered by Metformin and Liraglutide Treatment in A High-Fat High-Sugar Diet Rat Model
Marin Kuharić
; Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Vedrana Ivić
; Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Milorad Zjalić
; Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Anita Matić
; Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Ines Drenjančević
; Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Sandor G. Vari
; International Research and Innovation in Medicine Program, Cedars-Sinai Medical Center, Los Angeles, California, USA
Aleksandar Včev
; Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Marija Heffer
; Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
Abstract
Insulin resistance has many deleterious effects on the central nervous system, including
the initiation and potentiation of neurodegeneration. While the pathogenesis of Alzheimer’s disease
has been extensively researched with many insights into the effects of amyloids and neurofibrillary tangles,
the connection between the two pathogenic entities has not yet been fully elucidated. Gangliosides
are commonly found in neuronal membranes and myelin, specifically in lipid rafts that have been linked
to pathological amyloidogenesis. In this study, 64 Sprague Dawley rats with equal sex distribution were
separated into four sex-specific groups, as follows: control group on standard diet; group on high-fat,
high-sugar diet (HFHSD); group on HFHSD treated with metformin; and group on HFHSD treated
with liraglutide. Free-floating immunohistochemistry of the rat hippocampi was performed to analyze
group-specific and sex-specific changes in the composition of the four most common gangliosides found
in neuronal membranes and myelin sheaths, GM1, GD1a, GD1b and GT1b. The groups on HFHSD
showed glucose tolerance impairment and body weight increase at the end of the experiment, whereas
the groups treated with pharmacotherapeutics had better insulin sensitivity and decreases in body weight
by the end of the experiment. Most changes were observed for GM1 and GD1b. Positive immunoreactivity
for GM1 was observed in the male group treated with liraglutide in regions where it is not physiologically
found. The changes observed following HFHSD and liraglutide treatment were suggestive
of ganglioside restructuring that might have implications on pathological amyloidogenesis. Metformin
treatment did not significantly alter the hippocampal ganglioside composition in either sex.
Keywords
Ganglioside; Hippocampus; Insulin resistance; Liraglutide; Metformin; Neurodegeneration
Hrčak ID:
307278
URI
Publication date:
1.4.2023.
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