Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2019; 65(4): 31-40


T.M. Kovalenko1, I.O. Osadchenko1, D.R. Shepilov1, K.G. Smozhanyk1, D.V. Muraviova2, G.O. Ushakova2, N. Marungruang3, O. Prykhodko3, F. Hallenius3, G.G. Skibo1

  1. Bogomoletz Institute of Physiology, Kyiv, Ukraine
  2. Oles Honchar Dnipro National University, Ukraine
  3. Lund University, Sweden


The morphological and biochemical studies of the hippocampal CA1 area in ApoE-deficient mice under the conditions of dietary intake (8 weeks) with low (LF) and high (HF) fat content were performed. Methods of immunohistochemistry, light and electron microscopy, immunoassay and morphometric as well as statistical analyses were used. It was revealed that the morpho-functional state of the nerve cells of the hippocampus ApoE-/- mice highly depends on the fat content of the diet. A higher degree of neuroinflammation was observed in the LF-group than in the control and HF-groups, which was manifested in reactive astro- and microgliosis. The number of undamaged pyramidal neurons in the CA1 area of the hippocampus ApoE-/- mice in the LF-group significantly decreased compared to the control group and the HF-group. In animals with LF- and HF-diet the density of synaptic terminals, the number of mitochondria in them, as well as the concentration of cellular adhesion molecules were decreased. It was suggested that synaptogenesis and synaptic plasticity in higher degree depended on the shortage of аpolipoprotein E than on the fat content in the diet.

Keywords: ApoE-knockout mice, hippocampal structure, low and high fat diets


  1. Yaffe K. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004 Nov 10;292(18):2237-42. CrossRef PubMed
  3. Kolovou G, Anagnostopoulou K, Mikhailidis DP, Cokkinos DV. Apolipoprotein E knockout models. Curr Pharm Des. 2008;14(4):338-51. CrossRef PubMed
  5. Vance JE. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis Model Mech. 2012 Nov;5(6):746-55. CrossRef PubMed PubMedCentral
  7. Vance JE, Hayashi H. Formation and function of apolipoprotein E-containing lipoproteins in the nervous system. Biochim Biophys Acta. 2010 Aug;1801(8):806-18. CrossRef PubMed
  9. Janssen CI, Jansen D, Mutsaers MP, Dederen PJ, Geenen B, Mulder MT, Kiliaan AJ. The effect of a high-fat diet on brain plasticity, inflammation and cognition in female ApoE4-knockin and ApoE-knockout mice. PLoS One. 2016 May 12;11(5):e0155307. CrossRef PubMed PubMedCentral
  11. Famer D, Wahlund LO, Crisby M. Rosuvastatin reduces microglia in the brain of wild type and ApoE knockout mice on a high cholesterol diet; implications for prevention of stroke and AD. Biochem Biophys Res Commun. 2010 Nov 12;402(2):367-72. CrossRef PubMed
  13. Lo Sasso G, Schlage WK, Boué S, Veljkovic E, Peitsch MC, Hoeng J. The Apoe(-/-) mouse model: a suitable model to study cardiovascular and respiratory diseases in the context of cigarette smoke exposure and harm reduction. J Transl Med. 2016 May 20;14(1):146. CrossRef PubMed PubMedCentral
  15. Lane-Donovan C, Wong WM, Durakoglugil MS, Wasser CR, Jiang S, Xian X, Herz J. Genetic restoration of plasma ApoE improves cognition and partially restores synaptic defects in ApoE-deficient mice. J Neurosci. 2016 Sep 28;36(39):10141-50. CrossRef PubMed PubMedCentral
  17. Wang X, Michaelis EK. Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci. 2010 Mar 30;2:12. CrossRef PubMed PubMedCentral
  19. Weakley B. A beginner's handbook in biological electron microscopy. M.: Mir; 1975. [Russian].
  21. Ushakova GA, Berezin VA, Skibo GG. Neural cell adhesion molecule (N-CAM) distribution may predict the effect of neurotoxins on the brain. Toxicon. 1995;33(4):577-81. CrossRef  
  22. Crisby M, Rahman SMA, Sylvén C, Winblad B, & Schultzberg M. (2004). Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice. Neurosci Letters. 2004 369(2): 87-92. CrossRef PubMed
  24. Verkhratsky A, Rodríguez JJ, Parpura V. Astroglia in neurological diseases. Future Neurol. 2013 Mar 1;8(2):149-58. CrossRef PubMed PubMedCentral
  26. Elhaik Goldman S, Goez D, Last D, Naor S, Liraz Zaltsman S, Sharvit-Ginon I, Cooper I. High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model. Aging Cell. 2018 Oct;17(5): e12818. CrossRef PubMed PubMedCentral
  28. Chan YK, Brar MS, Kirjavainen PV, Chen Y, Peng J, Li D, El-Nezami H. High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE-/- mice. BMC Microbiology. 2016 Nov 8;16(1): 264. CrossRef PubMed PubMedCentral
  30. Kasahara K, Tanoue T, Yamashita T, Yodoi K, Matsumoto T, Emoto T, Hirata K. Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. J Lipid Res. 2017 Mar;58(3): 519-28. CrossRef PubMed PubMedCentral
  32. Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets. 2007 Jun;6(3):219-33. CrossRef  
  33. Gómez-Pinedo U, Duran-Moreno M, Sirerol-Piquer S, Matias-Guiu J. Myelin changes in Alexander disease. Neurologia. 2018;33(8):526-33. CrossRef PubMed
  35. Cambon K, Hansen SM., Venero C, Herrero AI, Skibo G, Berezin V, Bock E, Sandi C. A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci. 2004 Apr 28;24(17):4197-204. CrossRef PubMed PubMedCentral
  37. Nunes VS, Cazita PM, Catanozi S, Nakandakare ER, Quintão ECR. Decreased content, rate of synthesis and export of cholesterol in the brain of apoE knockout mice. J Bioenergetics and Biomembranes. 2018 Aug;50(4): 283-7. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2023.