Anat Cell Biol.  2014 Jun;47(2):117-126. 10.5115/acb.2014.47.2.117.

A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats

• Abo El-Khair DM
• El-Safti F
• Nooh HZ
• El-Mehi AE

• KMID: 1882582
• DOI: http://doi.org/10.5115/acb.2014.47.2.117

Abstract

Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

Keyword

Cholesterol; Aging; Cornu Ammonis; Hippocampus; Pyramidal cells

MeSH Terms

Adult*
Aging
Animals
Astrocytes
Blood Vessels
Cholesterol*
Dementia
Diet*
Hippocampus
Humans
Learning
Life Style
Male
Memory
Pyramidal Cells
Rats*
Cholesterol

Figure

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  Fig. 1 Mean body weight of the experimental groups (in grams) at the start and the end of the experiment. bal., balanced; chol., cholesterol. *Significant difference (P<0.05).

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  Fig. 2 A section of hippocampus showing: (A) adult balanced diet fed rats composed of four areas: CA1, CA2, CA3, and CA4. There is a narrow hippocampus sulcus (HS), and dentate gyrus (DG). (B) Aged balanced diet fed rats shows, apparent decrease in the hippocampus thickness compared with adult balanced. Also, there is increased vascularization (arrows) inside the hippocampus sulcus. (C) Adult cholesterol diet fed rats shows, vascularization (arrows) and peripheral degeneration (thin arrows). (D) Aged cholesterol diet fed rats shows, multiple vacuolations (V) especially in CA1 area, fibrotic meninges (arrowhead) and peripheral degeneration (thin arrows). LV, lateral ventricle (H&E, ×40).

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  Fig. 3 CA1 area of hippocampus. (A) Adult balanced diet fed rats shows, molecular (M), pyramidal (P), and polymorphic (Po) layers. The glial cells (arrowheads) and capillaries (c) are scattered inside molecular and polymorphic layers. (B) Aged balanced diet fed rats shows, slight disorganization of the pyramidal cell layer (P) with presence of many capillaries (c) and neuralgia cells (arrowheads). (C) Adult cholesterol diet fed rats shows, disorganization, degeneration and shrinkage of all pyramidal cells and presence of dispersed small vacuolations (V). (D) Aged cholesterol diet fed rats shows, shrinkage and darkness of all pyramidal cells, vacuolations (V) and massive neurogliosis and degeneration (thin arrows) in the molecular layer (M) (A-D, H&E, ×100).

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  Fig. 4 CA1 area of hippocampus. (A) Adult balanced diet fed rats shows, well organized pyramidal cells. There are different types of the neuralgia cells are scattered inside the neuropil matrix such as astrocytes (tailed arrowhead) with small vesicular nuclei; oligodendroglia (hollow arrowhead) with small dark nuclei and perinuclear halos and microglia with rod-shaped nuclei (triangle arrowhead). P, pyramidal layer; Po, polymorphic layer. (B) Aged balanced diet fed rats shows, apparent decrease in the number of pyramidal cells with presence of some shrunken degenerated cells (black arrows). There is slight vacuolations (spongiosis) (S) in the neuropil of molecular layer (M). (C) Adult cholesterol diet fed rats shows, hyalinized pyramidal cells with eccentric nuclei (black arrow), many glial cells (arrowheads) and presence of both thickened and attenuated capillaries (c). (D) Aged cholesterol diet fed rats shows, increased number of thickened and attenuated capillaries (c) with gliosis (arrowheads) (A-D, H&E, ×400).

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  Fig. 5 CA1 area of hippocampus. (A) Adult balanced diet fed rats shows, typical pyramidal cells (dashed lines) with triangular bodies, basophilic rim of cytoplasm, large vesicular nuclei (N) and prominent nucleoli. The oligodendroglia cell (arrowhead) lies adjacent to the pyramidal cell membrane. (B, C) Aged balanced diet fed rats shows, a senile neuritic plaque (dashed circle), apoptotic oligodendroglia (arrowheads) and the pyramidal cells either sclerotic (thin arrow) or dark shrunken (thick arrow). (D) Adult cholesterol diet fed rats shows, eosinophilic degenerated pyramidal cell with disintegrated axon (thick arrow), other pyramidal cells become swelling (thin arrow). Also, there are eosinophilic Hirano body (curved arrow) and Lipofuscin pigmentation (corrugated arrow). (E) Aged cholesterol diet fed rats shows, extra neural Hirano bodies (arrows), both intracellular tangles (triangle arrowhead) and granulovacuolar degeneration (tailed arrowhead), Lewy's body (crossed arrow) and apoptotic oligodendroglia (hollow arrowhead) (A-E, H&E, ×1,000).

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  Fig. 6 CA1 area pyramidal cells. (A) Adult balanced diet fed rats shows with triangle cell body with nodded axon and multiple branched dendrites with spines (inset) (B). (B) Aged balanced diet fed rats with sclerotic cell membrane, short hollow axon and few non branched, hollow, spineless dendrites (inset). (C) Adult cholesterol diet fed rats shows, with ballooned non-dendritic body and disintegrated axon. (D) Aged cholesterol diet fed rats shows, with either clumped or ballooned non-dendritic body and severely disintegrated axon (A-D, Golgi Cox, ×1,000).

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  Fig. 7 CA1 area of hippocampus. (A) Adult balanced diet fed rats shows, strong (++++) positive touildine blue expression (arrows). (B, C) Aged balanced diet fed rats and adult cholesterol diet fed rats show, week positive (++) toluidine blue expression (arrows). (D) Aged cholesterol diet fed rats shows, very week (+) positive touildine blue expression in aged cholesterol (arrows) (A-D, toluidine blue, ×1,000).

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  Fig. 8 CA1 area of hippocampus. (A) Adult balanced diet fed rats shows, slight positive brown glial Fibrillary acidic protein (GFAP) reaction small non branched dispersed astrocytes (arrows). (B) Aged balanced diet fed rats shows, positive brown expression of GFAP in small branched astrocytes (arrow). (C) Adult cholesterol diet fed rats shows, positive brown expression of GFAP in large branched astrocytes (arrows). (D) Aged cholesterol diet fed rats shows, dense positive brown expression of GFAP in large branched astrocytes (arrows) (A-D, GFAP, ×1,000).

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