Influence of Fructose-Fat Diet on Age-Related Morphological Changes in Rats Visual Cortex

The aim was to study the morphological changes in the visual cortex of the brain in young and old rats treated with a fructose-fat diet (FFD). Material and methods. The study was carried out on male Wistar rats, divided into the following groups: 1st (n=14) – intact 6-month-old rats received a standard diet; 2nd (n=14) – 6-month-old rats received a fructose-fat diet (FFD) for 90 days (from 3 months of age); 3rd (n = 14) – intact 18-month-old rats received a standard diet; 4th (n = 14) – 18-month-old rats received the FFD for 90 days (from 15 months of age). Histological sections were Nissl stained. Immunohistochemical reaction was performed to detect the expression of vascular endothelial growth factor (VEGF). In layers II, IV and V of the primary visual cortex, the percentage of normochromic and altered neurons and the number of gliocytes in 1 mm2 of section were calculated. Differences between groups were determined using the Kruskal–Wallis multiple comparison test. Results. In Morphological changes in the visual cortex in 18-month-old rats were most pronounced in layers IV and V and, in addition to reversible neuronal disorders, were characterized by total chromatolysis and vacuolization of the cytoplasm. In 6-month-old rats on a FFD, the most pronounced increase in hyperchromic neurons with shrinkage was observed in layer IV. In 18-month-old animals, pathological changes in neurocytes were found in all studied layers of the primary visual cortex, and pronounced signs of neuronophagia and gliosis were noted. In 18-month-old intact rats and 6- and 18-month-old rats on a FFD, vascular congestion and perivascular edema and pronounced expression of VEGF were detected. Conclusion. FFD enhances age-related changes in the visual cortex of rats, manifested by vascular disorders, degenerative changes in neurons and glial hyperreactivity.

1. Bogolepov NN. Ul'trastruktura mozga pri gipoksii. M.: Meditsina; 1979. 167. (in Russ.).

2. Gribanov AV, Dzhos YuS, Deryabina IN, i dr. Starenie golovnogo mozga cheloveka: morfofunktsional'nye aspekty. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. Spetsvypuski. 2017;117(1-2):3-7. (in Russ.). doi: 10.17116/jnevro2017117123-7.

3. Logvinov SV, Mustafina LR, Kurbatov BK, i dr. Vliyanie vysokouglevodnoi vysokozhirovoi diety na setchatku molodykh i starykh krys. Byulleten' sibirskoi meditsiny. 2022;21(4):98-104. (in Russ.). doi: 10.20538/1682-0363-2022-4-98-104.

4. Magnaeva AS, Gulevskaya TS, Anufriev PL. Morfologicheskaya kharakteristika nervnoi tkani golovnogo mozga pri starenii. Arkhiv patologii. 2022; 84(4):20-28. (in Russ.). doi: 10.17116/patol20228404120.

5. Makar'eva LM, Akulinin VA, Stepanov SS, i dr. Morfologicheskoe i morfometricheskoe opisanie neironov sensomotornoi kory golovnogo mozga krys posle perevyazki obshchikh sonnykh arterii. Zhurnal anatomii i gistopatologii. 2022;11(1):49-58. (in Russ.). doi: 10.18499/2225-7357-2022-11-1-49-58.

6. Nadei OV, Ivanova TI, Sufieva DA, Agalakova NI. Morfologicheskie izmeneniya neironov gippokampa krys kak rezul'tat izbytochnogo potrebleniya ftora. Zhurnal anatomii i gistopatologii. 2020;9(2):53-60. (in Russ.). doi: 10.18499/2225-7357-2020-9-2-53-60.

7. Romanova OL, Golubev AM, Churilov AA, Sundukov DV, Kislov MA, Ershov AV. Povrezhdeniya neironov kory golovnogo mozga pri ostrykh otravleniyakh baklofenom i ego cochetaniem s etilovym spirtom. Sudebnaya meditsina. 2022;8(4):15-24. (in Russ.). doi: 10.17816/fm431.

8. Bianco L, Arrigo A, Aragona E, et al. Neuroinflammation and neurodegeneration in diabetic retinopathy. Front Aging Neurosci. 2022;14:937999. doi: 10.3389/fnagi.2022.937999.

9. Buchanan J, da Costa NM, Cheadle L. Emerging roles of oligodendrocyte precursor cells in neural circuit development and remodeling. Trends Neurosci. 2023;46(8):628-639. doi: 10.1016/j.tins.2023.05.007.

10. Calvo PM, Hernández RG, Pastor AM, de la Cruz RR. VEGF and Neuronal Survival. Neuroscientist. 2024;30(1):71-86. doi: 10.1177/10738584221120803.

11. Chen F, Yi WM, Wang SY, Yuan MH, Wen J, Li HY, Zou Q, Liu S, Cai ZY. A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling. Front. Neurosci. 2022;16:978431. doi: 10.3389/fnins.2022.978431.

12. Damisah EC, Hill RA, Rai A, Chen F, Rothlin CV, Ghosh S, Grutzendler J. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Sci Adv. 2020 Jun 26;6(26):eaba3239. doi: 10.1126/sciadv.aba3239.

13. Hamanaka G, Hernández IC, Takase H, Ishikawa H, Benboujja F, Kimura S, Fukuda N, Guo S, Lok J, Lo EH, Arai K. Myelination- and migration-associated genes are downregulated after phagocytosis in cultured oligodendrocyte precursor cells. J Neurochem. 2023 Nov;167(4):571-581. doi: 10.1111/jnc.15994.

14. Hayden MR. The Brain Endothelial Cell Glycocalyx Plays a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Life (Basel). 2023;13(10):1955. doi: 10.3390/life13101955.

15. Kalaria R, Ferrer I, Love S. Vascular disease, hypoxia and related conditions In: Love S, Budka H, Ironside JW, Perry A, eds. Greenfield's neuropathology. Vol 1 9th ed. Boca Raton, USA: CRC Press; 2015:87–88.

16. Keeling E, Lynn SA, Koh YM, et al. A High Fat "Western-style" Diet Induces AMD-Like Features in Wildtype Mice. Mol. Nutr. Food Res. 2022;66(11):e2100823. doi: 10.1002/mnfr.202100823.

17. Kullmann S, Schweizer F, Veit R, Fritsche A, Preissl H. Compromised white matter integrity in obesity. Obes Rev. 2015 Apr;16(4):273-81. doi: 10.1111/obr.12248.

18. Langley MR, Yoon H, Kim HN, Choi CI, Simon W, Kleppe L, Lanza IR, LeBrasseur NK, Matveyenko A, Scarisbrick IA. High fat diet consumption results in mitochondrial dysfunction, oxidative stress, and oligodendrocyte loss in the central nervous system. Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165630. doi: 10.1016/j.bbadis.2019.165630.

19. Lizarbe B, Soares AF, Larsson S, Duarte JMN. Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet. Front Neurosci. 2019;12:985. doi: 10.3389/fnins.2018.00985.

20. Martinelli I, Tayebati SK, Roy P, Micioni Di Bonaventura MV, Moruzzi M, Cifani C, Amenta F, Tomassoni D. Obesity-Related Brain Cholinergic System Impairment in High-Fat-Diet-Fed Rats. Nutrients. 2022 Mar 15;14(6):1243. doi: 10.3390/nu14061243.

21. Okabe K, Fukada H, Tai-Nagara I, Ando T, Honda T, Nakajima K, Takeda N, Fong GH, Ema M, Kubota Y. Neuron-derived VEGF contributes to cortical and hippocampal development independently of VEGFR1/2-mediated neurotrophism. Dev Biol. 2020 Mar 15;459(2):65-71. doi: 10.1016/j.ydbio.2019.11.016.

22. Onyango AN Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance. Oxid. Med. Cell. Longev. 2018;2018:4321714. doi: 10.1155/2018/4321714.

23. Paz MC, Barcelona PF, Subirada PV, Ridano ME, Chiabrando GA, Castro C, Sánchez MC. Metabolic Syndrome Triggered by Fructose Diet Impairs Neuronal Function and Vascular Integrity in ApoE-KO Mouse Retinas: Implications of Autophagy Deficient Activation. Front Cell Dev Biol. 2020 Oct 8;8:573987. doi: 10.3389/fcell.2020.573987.

24. Rattner A, Williams J, Nathans J. Roles of HIFs and VEGF in angiogenesis in the retina and brain. J. Clin. Invest. 2019;129(9):3807-3820. doi: 10.1172/JCI126655.

25. Rojas-Gutierrez E, Muñoz-Arenas G, Treviño S, Alzheimer’s disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration. Synapse. 2017;71(10):e21990. doi: 10.1002/syn.21990.

26. Rossino MG, Dal Monte M, Casini G. Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy. Front Neurosci. 2019;13:1172. doi: 10.3389/fnins.2019.01172.

27. Seabrook LT, Peterson CS, Noble D, Sobey M, Tayyab T, Kenney T, Judge AK, Armstrong M, Lin S, Borgland SL. Short- and Long-Term High-Fat Diet Exposure Differentially Alters Phasic and Tonic GABAergic Signaling onto Lateral Orbitofrontal Pyramidal Neurons. J Neurosci. 2023 Dec 13;43(50):8582-8595. doi: 10.1523/JNEUROSCI.0831-23.2023.

28. Valcarcel-Ares MN, Tucsek Z, Kiss T, Giles CB, Tarantini S, Yabluchanskiy A, Balasubramanian P, Gautam T, Galvan V, Ballabh P, Richardson A, Freeman WM, Wren JD, Deak F, Ungvari Z, Csiszar A. Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline. J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):290-298. doi: 10.1093/gerona/gly127.

29. Vidal E, Lalarme E, Maire MA, Febvret V, Grégoire S, Gambert S, Acar N, Bretillon L. Early impairments in the retina of rats fed with high fructose/high fat diet are associated with glucose metabolism deregulation but not dyslipidaemia. Sci Rep. 2019 Apr 12;9(1):5997. doi: 10.1038/s41598-019-42528-9.

30. Wang XL, Li L. Microglia Regulate Neuronal Circuits in Homeostatic and High-Fat Diet-Induced Inflammatory Conditions. Front. Cell. Neurosci. 2021;15:722028. doi: 10.3389/fncel.2021.722028.