Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density
Open accessAbstract
Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive function; however, the in vivo effect of enhanced Reelin signaling on cognitive function and synaptic plasticity in wild-type mice is unknown. The present studies test the hypothesis that in vivo enhancement of Reelin signaling can alter synaptic plasticity and ultimately influence processes of learning and memory. Purified recombinant Reelin was injected bilaterally into the ventricles of wild-type mice. We demonstrate that a single in vivo injection of Reelin increased activation of adaptor protein Disabled-1 and cAMP-response element binding protein after 15 min. These changes correlated with increased dendritic spine density, increased hippocampal CA1 long-term potentiation (LTP), and enhanced performance in associative and spatial learning and memory. The present study suggests that an acute elevation of in vivo Reelin can have long-term effects on synaptic function and cognitive ability in wild-type mice.
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ApoER2 mediates Reelin signaling to enhance learning and memory in mice.
“Since loss of ApoER2 impairs LTP, and since ApoER2 mediates Reelin signaling to enhance learning and memory in mice (Bosch et al., 2016; Niu et al., 2008; Rogers et al., 2011), it has been suggested that increased ApoER2 expression would be beneficial.”
From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Rogers et al., 2011
The Results show that Reelin did not increase Dab1 or CREB activation in ApoER2-knockout mice, and the Discussion describes the in vivo signaling as ApoER2-dependent. The paper also reports enhanced learning and memory after Reelin injection in wild-type mice, but does not show that ApoER2 is required for that behavioral improvement. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIntraventricular injection of Reelin in mice improves learning and memory.
“intraventricular injection of Reelin in mice improves learning and memory [30].”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [30]
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“This effect is mirrored in vivo by the finding that intraventricular injection of Reelin in mice improves learning and memory [30].”
ResultMore than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
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- Authors
- Rogers, J. T., Rusiana, I., Trotter, J., Zhao, L., Donaldson, E., Pak, D. T. S., Babus, L. W., Peters, M., Banko, J. L., Chavis, P., Rebeck, G. W., Hoe, H.-S., & Weeber, E. J.
- Affiliations
- University of South Florida (US)
- Vanderbilt University Medical Center (US)
- Georgetown University (US)
- Inserm (FR)
- ORCID
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-08-18
- Volume
- 18
- Issue
- 9
- Pages
- 558-564
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC3166788
- OpenAlex
- W2125925423
- Cited by
- 181
- References
- 38
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 11 · 2023: 12 · 2022: 11 · 2021: 12 · 2020: 21 · 2019: 7 · 2018: 5 · 2017: 14 · 2016: 26 · 2015: 13 · 2014: 11 · 2013: 15 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01AG030128, R01AG035379)
- National Institute of Neurological Disorders and Stroke (R01NS048085)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- reelin, synaptic plasticity, dendritic spine density, hippocampal CA1, long-term potentiation, learning and memory, Disabled-1, CREB, cognitive enhancement
- MeSH terms
- Reelin Protein, Action Potentials, Animals, Brain, Cognition, Conditioning, Psychological, Exploratory Behavior, Fear, Humans, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Silver Staining, Maze Learning, Excitatory Postsynaptic Potentials, Dendritic Spines, CREB-Binding Protein, Mice, HEK293 Cells
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