Related Experiment Video
Updated: Jul 13, 2026
Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Brain-specific ORP6 deficiency in mice disrupts systemic lipid metabolism and impairs hippocampal-dependent learning
Arlette A Kasongo1, Benjamin Bhunu2, Dominique M Boucher1
1Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Rd., Ottawa, ON K1H 8M5, Canada; University of Ottawa Heart Institute, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada.
Abstract:
Cholesterol homeostasis in the central nervous system is essential for neuronal health and cognitive function. Among the oxysterol-binding protein (OSBP)-related proteins (ORPs), a conserved family of lipid transfer proteins, ORP6 has emerged as a brain-enriched isoform with potential roles in metabolic regulation and neuroprotection.Here, we generated a brain-specific Osbpl6 conditional knockout (Osbpl6Δbrain) to investigate its contribution to lipid metabolism and brain function. Loss of ORP6 in the brain lead to increased body weight and higher total cholesterol, driven primarily by increased low-density lipoprotein (LDL) cholesterol.Within the brain, Osbpl6Δbrain mice displayed elevated levels of amyloid beta oligomers (AβO) and impaired hippocampal-dependent learning and memory, as assessed by the Morris water maze and contextual fear conditioning. Together, these results identify brain ORP6 as a key regulator of lipid homeostasis, underscoring its essential role in maintaining cholesterol balance and protecting cognitive function.
