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Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr −/− mouse experimental model
Abstract
Although epidemiological studies have reported an association between hypercholesterolemia and mood disorders, there is a lack of data regarding depressive-like behavior in animal models of hypercholesterolemia. To address these questions, we assessed depressive-like behavior and hippocampal and cortical monoaminergic metabolism in three-month-old, low-density lipoprotein receptor knockout (LDLr(-/-)) and C57BL/6 wild-type mice. The LDLr(-/-) mice exhibited depressive-like behavior in the sucrose preference test, splash test, and tail suspension test. Increased monoamine oxidase (MAO) A and B activity was evidenced in the hippocampus of LDLr(-/-) mice. Furthermore, to address whether or not cholesterol modulates MAO activity, we exposed SH-SY5Y human neuroblastoma cells to human isolated low-density lipoprotein (LDL). Notably, LDL increased the activity of MAO-A and stimulated the reactive species generation in vitro. These findings indicate that depressive-like behavior in hypercholesterolemic mice is accompanied by alterations in the monoaminergic metabolism, providing new evidence about the association between hypercholesterolemia and depression.
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“In parallel, studies examining the effects of native (non‐oxidized) and oxidized LDL (ox‐LDL) on brain cells have reported that LDL exposure in primary cortical neurons and neuronal cell lines disrupts endolysosomal function, increases amyloid‐β production, reduces synaptophysin levels, and induces mitochondrial dysfunction and oxidative stress (Engel et al. 2016; Hui et al. 2012; Yamchuen et al.”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Engel et al. 2016
In the citing paper
“In parallel, studies examining the effects of native (non‐oxidized) and oxidized LDL (ox‐LDL) on brain cells have reported that LDL exposure in primary cortical neurons and neuronal cell lines disrupts endolysosomal function, increases amyloid‐β production, reduces synaptophysin levels, and induces mitochondrial dysfunction and oxidative stress (Engel et al. 2016; Hui et al. 2012; Yamchuen et al.”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Engel et al. 2016
In the citing paper
“In parallel, studies examining the effects of native (non‐oxidized) and oxidized LDL (ox‐LDL) on brain cells have reported that LDL exposure in primary cortical neurons and neuronal cell lines disrupts endolysosomal function, increases amyloid‐β production, reduces synaptophysin levels, and induces mitochondrial dysfunction and oxidative stress (Engel et al. 2016; Hui et al. 2012; Yamchuen et al.”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Engel et al. 2016
In the citing paper
“In parallel, studies examining the effects of native (non‐oxidized) and oxidized LDL (ox‐LDL) on brain cells have reported that LDL exposure in primary cortical neurons and neuronal cell lines disrupts endolysosomal function, increases amyloid‐β production, reduces synaptophysin levels, and induces mitochondrial dysfunction and oxidative stress (Engel et al. 2016; Hui et al. 2012; Yamchuen et al.”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Engel et al. 2016
In the citing paper
“In parallel, studies examining the effects of native (non‐oxidized) and oxidized LDL (ox‐LDL) on brain cells have reported that LDL exposure in primary cortical neurons and neuronal cell lines disrupts endolysosomal function, increases amyloid‐β production, reduces synaptophysin levels, and induces mitochondrial dysfunction and oxidative stress (Engel et al. 2016; Hui et al. 2012; Yamchuen et al.”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Engel et al. 2016
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Metadata
- Authors
- Engel, D. F., de Oliveira, J., Lopes, J. B., Santos, D. B., Moreira, E. L. G., Farina, M., Rodrigues, A. L. S., de Souza Brocardo, P., & de Bem, A. F.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 311
- Pages
- 31-38
- ISSN
- 0166-4328
- Cited by
- 44
- References
- 9
- Language
- en
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
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