Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

• Published in: Brain communications 2023, Vol.5 (2), p.fcad059-fcad059
• Main Authors: Andrade, Mayara M, Fernandes, Caroline, Forny-Germano, Leticia, Gonçalves, Rafaella A, Gomes, Michelle, Castro-Fonseca, Emily, Ramos-Lobo, Angela M, Tovar-Moll, Fernanda, Andrade-Moraes, Carlos Humberto, Donato, Jose, De Felice, Fernanda G
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2632-1297; 2632-1297
• DOI: 10.1093/braincomms/fcad059

Abstract Obesity is defined as abnormal or excessive fat accumulation that may impair health and is a risk factor for developing other diseases, such as type 2 diabetes and cardiovascular disorder. Obesity is also associated with structural and functional alterations in the brain, and this condition has been shown to increase the risk of Alzheimer’s disease. However, while obesity has been associated with neurodegenerative processes, its impact on brain cell composition remains to be determined. In the current study, we used the isotropic fractionator method to determine the absolute composition of neuronal and non-neuronal cells in different brain regions of the genetic mouse models of obesity Lepob/ob and LepRNull/Null. Our results show that 10- to 12-month-old female Lepob/ob and LepRNull/Null mice have reduced neuronal number and density in the hippocampus compared to C57BL/6 wild-type mice. Furthermore, LepRNull/Null mice have increased density of non-neuronal cells, mainly glial cells, in the hippocampus, frontal cortex and hypothalamus compared to wild-type or Lepob/ob mice, indicating enhanced inflammatory responses in different brain regions of the LepRNull/Null model. Collectively, our findings suggest that obesity might cause changes in brain cell composition that are associated with neurodegenerative and inflammatory processes in different brain regions of female mice. This study identifies neuronal loss in the hippocampus and frontal cortex of two mouse models of obesity (Lepob/ob and LepRNull/Null) using the isotropic fractionator. LepRNull/Null displayed increased non-neuronal cells, primarily glial cells, in the hippocampus, frontal cortex and hypothalamus. Quantitative measures showed that LepRNull/Null exhibits aggravated neurodegeneration when compared to Lepob/ob. Graphical Abstract Graphical Abstract