Increased astrocyte representation in the hippocampus of 5xFAD mice

  • Violeta Jovanović Medicinski fakultet u Beogradu
  • Jelica Despotovic University of Belgrade Faculty of Medicine
  • Mario Balo University of Belgrade Faculty of Medicine
  • doc. dr Ivan Zaletel University of Belgrade Faculty of Medicine
  • doc. dr Sanja Despotovic University of Belgrade Faculty of Medicine
  • prof. dr Nela Puskas University of Belgrade Faculty of Medicine
Keywords: Alzheimer's disease, 5xFAD, hippocampus, astrocytes, GFAP

Abstract


Introduction: Alzheimer's disease is the most common neurodegenerative disorder, characterized by the formation of amyloid plaques and the neurofibrillary tangles in the brain of a sick person, leading to neuronal damage and loss. Activation of astrocytes and astrogliosis occurs along with this process. Due to ethical limitations in working with human tissue, numerous transgenic animal models have been developed to study the pathogenesis of this processes. Early Aβ deposition is observed in the cortex and the hippocampus.

Aim: The aim of this study was to determine the difference in the presence of GFAP positive cells in the hippocampus between transgenic 5xFAD mice aged 36 weeks and their corresponding controls.

Material and methods: The 5xFAD mice model of Alzheimer's disease was used, characterized by early formation of amyloid plaques but without the presence of a neurofibrillar tangles. Transgenic and control animals were sacrificed at 36 weeks of age. The visualization of GFAP-positive cells in the hippocampus of their brains was done by using immunohistochemistry and antibodie for glial fibrillary acidic protein – GFAP, the major marker of astrocytes. Quantification of immunoreactivity was done by using Icy software system.

Results: There was a statistically significant difference in the expression of GFAP in the dentate gyrus and the granular zone of the hippocampus between the transgenic and control group at 36 weeks of age, while significant change in the CA1-3 regions was not observed between investigated groups.

Conclusion: Obtained results confirm involvement of astrogliosis in the pathophysiology of Alzheimer's disease, but also indicate an earlier occurrence of astrogliosis in the dentate gyrus and granular zone in relation to other regions of the hippocampus in the 36-week-old 5xFAD mice.

References

1. Forny-Germano L, Lyra e Silva NM, Batista AF, Brito-Moreira J, Gralle M, Boehnke SE et al. Alzheimer’s disease-like pathology induced by amyloid-beta oligomers in nonhuman primates. J Neurosci. 2014; 34(41): 13629–13643.
2. Zhiyou C, Cheng-Qun W, Zhou L. Astrocyte and Alzheimer’s disease. Journal of Neurology. 2017; 267: 2068-2074.
3. Voss JL, Bridge DJ, Cohen NJ, Walker JA. A Closer Look at the Hippocampus and Memory. Trends Cogn Sci. 2017; 21: 577-588.
4. Schott JM, Fox NC, Frost C, Scahill RI, Janssen JC, Chan D et al. Assessing the onset of structural change in familial Alzheimer’s disease. Ann Neurol. 2003; 87: 181-188.
5. Moodley KK, Chan D. The hippocampus in neurodegenerative disease. Front Neurol Neurosci. 2014; 44: 95-108.
6. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006; 34(41): 10129-40.
7. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010; 119(1): 7-35.
8. Jo WK, Law AC, Chung SK. Neglected co-star in the dementia drama: the putative roles of astrocytes in the pathogenesis of major neurodegenerative disorders. Mol Psychiatry. 2014; 19(2): 159-167.
9. Mancardi GL, Liwniez BH, Mandybur TI. Fibrous astrocytes in Alzheimer’s disease and senile dementia of Alzheimer’s type. Acta Neuropathol. 1983; 61(1): 76-80.
10. Lian H, Litvinchuk A, Chiang AC, Aithmitti N, Jankovsky JL, Zheng H. Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse models of Alzheimer’s Disease. J Neurosci. 2016; 34(41): 577-89.
11. Liu RX, Huang C, Bennett DA, Li H, Wang R. The characteristics of astrocyte on A clearance altered in Alzheimer’s disease were reversed by an anti-inflamatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate. Am J Transl Res. 2016; 8(10): 4082-4094.
12. Olsen M, Aguilar X, Sehlin D, Fang XT, Antoni G, Erlandsson A et al. Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s disease. Mol Imaging Biol. 2018; 20(4): 605-614.
13. Giarard SD, Jackuet M, Baranger K, Migliorati M, Escoffier G, Bernard A et al. Onset of hippocampus-dependent memory imparements in 5xFAD transgenic mouse model of Alzheimer’s disease. Hippocampus. 2014; 24: 762-772.
14. Lord A, Kalimo H, Eckman C, Zhang XQ, Lannfelt L, Nilsson LN. The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation and senile plaque formation in transgenic mice. Neurobiol Aging. 2006; 27(1): 67-77.
15. Hong I, Kang T, Yoo Y, Park R, Lee J, Lee S et al. Quantitative Proteomic Analysis of the Hippocampus in the 5xFAD Mouse Model at Early Stages of Alzheimer’s Disease Pathology. Journal of Alzheimer’s Disease. 2014; 36(2): 321–334.
Published
2021/07/21
Section
Original Scientific Paper