High levels of 27‑hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

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Loera‑Valencia, Raul and Vazquez‑Juarez, Erika and Muñoz Céspedes, Alberto and Gerenu, Gorka and Gómez‑Galán, Marta and Lindskog, Maria and DeFelipe, Javier and Cedazo‑Minguez, Angel and Merino‑Serrais, Paula (2021) High levels of 27‑hydroxycholesterol results in synaptic plasticity alterations in the hippocampus. Scientific Reports, 11 (3736). pp. 1-13. ISSN Electronic: 2045-2322

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Official URL: https://www.nature.com/articles/s41598-021-83008-3



Abstract

Alterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine longterm potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schafer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a signifcantly higher density of synaptopodinpositive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fne-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.


Item Type:Article
Uncontrolled Keywords:27‑hydroxycholesterol; Hippocampus
Subjects:Medical sciences > Biology > Neurosciences
ID Code:65958
Deposited On:03 Jun 2021 11:21
Last Modified:04 Jun 2021 06:50

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