RT Journal Article
T1 High levels of 27‑hydroxycholesterol resultsin synaptic plasticity alterations in the hippocampus
A1 Loera‑Valencia, Raul
A1 Vazquez‑Juarez, Erika
A1 Muñoz Céspedes, Alberto
A1 Gerenu, Gorka
A1 Gómez‑Galán, Marta
A1 Lindskog, Maria
A1 DeFelipe, Javier
A1 Cedazo‑Minguez, Angel
A1 Merino‑Serrais, Paula
AB 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.
PB Nature Research
SN Electronic: 2045-2322
YR 2021
FD 2021-02-12
LK https://hdl.handle.net/20.500.14352/8219
UL https://hdl.handle.net/20.500.14352/8219
LA eng
NO Ministerio de Ciencia, Innovación y Universidades (MCIU)
NO Centro de Investigación en Red sobre Enfermedades Neurodegenerativas
NO Programa Juan de la Cierva
NO EMBO Long-Term Fellowship
NO Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico)
NO Lindhés Advokatbyra Foundation (Stockholm)
NO Karolinska Institutet
DS Docta Complutense
RD 20 abr 2025