Brain Structure and Function

, Volume 214, Issue 2, pp 181–199

Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models

  • Jennifer I. Luebke
  • Christina M. Weaver
  • Anne B. Rocher
  • Alfredo Rodriguez
  • Johanna L. Crimins
  • Dara L. Dickstein
  • Susan L. Wearne
  • Patrick R. Hof
Original article

DOI: 10.1007/s00429-010-0244-2

Cite this article as:
Luebke, J.I., Weaver, C.M., Rocher, A.B. et al. Brain Struct Funct (2010) 214: 181. doi:10.1007/s00429-010-0244-2

Abstract

In neurodegenerative disorders, such as Alzheimer’s disease, neuronal dendrites and dendritic spines undergo significant pathological changes. Because of the determinant role of these highly dynamic structures in signaling by individual neurons and ultimately in the functionality of neuronal networks that mediate cognitive functions, a detailed understanding of these changes is of paramount importance. Mutant murine models, such as the Tg2576 APP mutant mouse and the rTg4510 tau mutant mouse have been developed to provide insight into pathogenesis involving the abnormal production and aggregation of amyloid and tau proteins, because of the key role that these proteins play in neurodegenerative disease. This review showcases the multidimensional approach taken by our collaborative group to increase understanding of pathological mechanisms in neurodegenerative disease using these mouse models. This approach includes analyses of empirical 3D morphological and electrophysiological data acquired from frontal cortical pyramidal neurons using confocal laser scanning microscopy and whole-cell patch-clamp recording techniques, combined with computational modeling methodologies. These collaborative studies are designed to shed insight on the repercussions of dystrophic changes in neocortical neurons, define the cellular phenotype of differential neuronal vulnerability in relevant models of neurodegenerative disease, and provide a basis upon which to develop meaningful therapeutic strategies aimed at preventing, reversing, or compensating for neurodegenerative changes in dementia.

Keywords

Alzheimer’s disease Amyloid Computational modeling Dendritic spine Tau Whole-cell patch-clamp 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jennifer I. Luebke
    • 1
  • Christina M. Weaver
    • 3
    • 4
  • Anne B. Rocher
    • 1
  • Alfredo Rodriguez
    • 2
    • 3
  • Johanna L. Crimins
    • 1
  • Dara L. Dickstein
    • 2
    • 3
  • Susan L. Wearne
    • 3
  • Patrick R. Hof
    • 2
    • 3
  1. 1.M949, Department of Anatomy and NeurobiologyBoston University School of MedicineBostonUSA
  2. 2.Department of NeuroscienceMount Sinai School of MedicineNew YorkUSA
  3. 3.Computational Neurobiology and Imaging CenterMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of Mathematics and Computer ScienceFranklin and Marshall CollegeLancasterUSA

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