Akademik Veri Yönetim Sistemi
36 th ECNP Congress, Barcelona, İspanya, 07 Ekim 2023 - 10 Nisan 2024, cilt.2, sa.813, ss.81
Hyperlipidemia is a metabolic disorder in which total cholesterol and low-density lipoprotein levels are increased, and high-density lipoprotein levels are
decreased. While hyperlipidemia has been characterized as a risk factor for
cardiovascular disease, this disorder has been considered a player in various
neurodegenerative diseases recently [1]. It is well-known that hyperlipidemia
induces peripheral inflammation, which is detrimental to peripheral tissues.
Interestingly, there is a growing body of evidence that hyperlipidemia-induced
inflammation also has an impact on the central nervous system. High-fat diet has
been shown to be a contributing factor to cognitive deficits [2]. However, how
high cholesterol levels lead to dysfunction in cognitive abilities is not wellstudied. Properly functioning neurons and synapses are crucial for the maintenance of synaptic communication in the central nervous system. Synaptic proteins are essential in mediating neurotransmission, neuronal signalling, synaptic
plasticity, and growth. These functions are critical for learning and memory
formation in the hippocampus and higher cognitive activities in the cortex [3]. It
is known that alterations in synaptic activity have effects on these processes. The
literature has shown that a high-fat diet negatively affects synaptic function in
different brain regions, including the hippocampus [4]. In the brain, various
areas are affected at varying rates by disruptions leading to a selective vulnerability in different brain regions. Yet, it has been suggested that highly myelinated
neurons like the ones in the hippocampus are more vulnerable to damage [5].
Additionally, the underlying molecular mechanisms of the impact of hyperlipidemia and varying cholesterol levels on synaptic integrity are not well-understood. In this study, we explored whether the hippocampus and cerebral cortex
are differentially affected by acute and chronic high cholesterol. We assessed
high cholesterol levels and their impact on synaptic integrity in the brain region
of the hippocampus and cerebral cortex in chow- and western diet-fed groups of
C57BL/6 and Apoe-/- mice, which carry a mutation that results in chronically
high cholesterol levels, by analyzing protein levels of synaptic proteins. Western
blot analysis of gephyrin (GEP), a presynaptic vesicle protein and postsynaptic
density-95 (PSD-95), as well as synaptophysin (SYP), a key synaptic vesicle
protein, was performed in synaptosomes derived from hippocampal and cortical
tissues of the mice. Our preliminary data indicated that PSD-95 significantly
increased in Apoe-/- mice hippocampus, but GEP and SYP remained stable.
Interestingly, there were no significant differences among synaptic protein levels
in the cerebral cortex region. These data suggest that higher cholesterol levels
alter the excitatory/inhibitory balance of hippocampal synapses, which likely
underlies some of the selective vulnerability of the hippocampus to neurodegenerative processes. Whereas the excitatory/inhibitory balance in the cortex
remained intact, suggesting a mechanism that selectively protects this region
from the onset of neurodegenerative disease. This project has been supported by
the TUBITAK 1001 Support Program with grant number 220S079