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ApoE Regulates the Development of Adult Newborn Hippocampal Neurons.

eNeuro | 2018

Adult hippocampal neurogenesis occurs throughout life and is believed to participate in cognitive functions such as learning and memory. A number of genes that regulate adult hippocampal neurogenesis have been identified, although most of these have been implicated in progenitor proliferation and survival, but not in the development into fully differentiated neurons. Among these genes, apolipoprotein E (ApoE) is particularly compelling because the human ApoE isoform E4 is a risk factor for the development of Alzheimer's disease, where hippocampal neurogenesis is reported to be dysfunctional. To investigate the effects of ApoE and its human isoforms on adult hippocampal neurogenesis and neuronal development, retroviruses carrying a GFP-expressing vector were injected into wild-type (WT), ApoE-deficient, and human targeted replacement (ApoE3 and ApoE4) mice to infect progenitors in the dentate gyrus and analyze the morphology of fully developed GFP-expressing neurons. Analysis of these adult-born neurons revealed significant decreases in the complexity of dendritic arborizations and spine density in ApoE-deficient mice compared with WT mice, as well as in ApoE4 mice compared with ApoE3. These findings demonstrate that ApoE deficiency and the ApoE4 human isoform both impair hippocampal neurogenesis and give insight into how ApoE may influence hippocampal-related neurological diseases.

Pubmed ID: 30079373 RIS Download

Additional research tools detected in this publication

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS095803
  • Agency: NINDS NIH HHS, United States
    Id: R56 NS089523

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This is a list of tools and resources that we have found mentioned in this publication.


GraphPad Prism (tool)

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FISHER (tool)

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Anti-Apolipoprotein E (antibody)

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Mus musculus with name B6.129P2-Apoetm3(APOE*4)Mae N8 from IMSR.

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Neurolucida (software resource)

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Anti-Apolipoprotein E (antibody)

RRID:AB_2258475

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AutoQuant (software resource)

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Stereo Investigator (software resource)

RRID:SCR_002526

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View all literature mentions

Stereo Investigator (software resource)

RRID:SCR_002526

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View all literature mentions

Neurolucida (software resource)

RRID:SCR_001775

Neurolucida is advanced scientific software for brain mapping, neuron reconstruction, anatomical mapping, and morphometry. Since its debut more than 20 years ago, Neurolucida has continued to evolve and has become the worldwide gold-standard for neuron reconstruction and 3D mapping. Neurolucida has the flexibility to handle data in many formats: using live images from digital or video cameras; stored image sets from confocal microscopes, electron microscopes, and scanning tomographic sources, or through the microscope oculars using the patented LucividTM. Neurolucida controls a motorized XYZ stage for integrated navigation through tissue sections, allowing for sophisticated analysis from many fields-of-view. Neurolucidas Serial Section Manager integrates unlimited sections into a single data file, maintaining each section in aligned 3D space for full quantitative analysis. Neurolucidas neuron tracing capabilities include 3D measurement and reconstruction of branching processes. Neurolucida also features sophisticated tools for mapping delineate and map anatomical regions for detailed morphometric analyses. Neurolucida uses advanced computer-controlled microscopy techniques to obtain accurate results and speed your work. Plug-in modules are available for confocal and MRI analysis, 3D solid modeling, and virtual slide creation. The user-friendly interface gives you rapid results, allowing you to acquire data and capture the full 3D extent of neurons and brain regions. You can reconstruct neurons or create 3D serial reconstructions directly from slides or acquired images, and Neurolucida offers full microscope control for brightfield, fluorescent, and confocal microscopes. Its added compatibility with 64-bit Microsoft Vista enables reconstructions with even larger images, image stacks, and virtual slides. Adding the Solid Modeling Module allows you to rotate and view your reconstructions in real time. Neurolucida is available in two separate versions Standard and Workstation. The Standard version enables control of microscope hardware, whereas the Workstation version is used for offline analysis away from the microscope. Neurolucida provides quantitative analysis with results presented in graphical or spreadsheet format exportable to Microsoft Excel. Overall, features include: - Tracing Neurons - Anatomical Mapping - Image Processing and Analysis Features - Editing - Morphometric Analysis - Hardware Integration - Cell Analysis - Visualization Features Sponsors: Neurolucida is supported by MBF Bioscience.

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RRID:SCR_015807

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View all literature mentions

AutoQuant (software resource)

RRID:SCR_002465

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View all literature mentions

C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

B6.129P2-Apoetm3(APOE*4)Mae N8 (organism)

RRID:IMSR_TAC:1549

Mus musculus with name B6.129P2-Apoetm3(APOE*4)Mae N8 from IMSR.

View all literature mentions

B6.129P2-Apoetm2(APOE*3)Mae N8 (organism)

RRID:IMSR_TAC:1548

Mus musculus with name B6.129P2-Apoetm2(APOE*3)Mae N8 from IMSR.

View all literature mentions

B6.129P2-Apoetm1Unc/J (organism)

RRID:IMSR_JAX:002052

Mus musculus with name B6.129P2-Apoetm1Unc/J from IMSR.

View all literature mentions

Anti-Apolipoprotein E (antibody)

RRID:AB_2258475

This polyclonal targets APOE

View all literature mentions