Back to Search
Start Over
Increasing CREB function in the CA1 region of dorsal hippocampus rescues the spatial memory deficits in a mouse model of Alzheimer's disease.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2011 Oct; Vol. 36 (11), pp. 2169-86. Date of Electronic Publication: 2011 Jul 06. - Publication Year :
- 2011
-
Abstract
- The principal defining feature of Alzheimer's disease (AD) is memory impairment. As the transcription factor CREB (cAMP/Ca(2+) responsive element-binding protein) is critical for memory formation across species, we investigated the role of CREB in a mouse model of AD. We found that TgCRND8 mice exhibit a profound impairment in the ability to form a spatial memory, a process that critically relies on the dorsal hippocampus. Perhaps contributing to this memory deficit, we observed additional deficits in the dorsal hippocampus of TgCRND8 mice in terms of (1) biochemistry (decreased CREB activation in the CA1 region), (2) neuronal structure (decreased spine density and dendritic complexity of CA1 pyramidal neurons), and (3) neuronal network activity (decreased arc mRNA levels following behavioral training). Locally and acutely increasing CREB function in the CA1 region of dorsal hippocampus of TgCRND8 mice was sufficient to restore function in each of these key domains (biochemistry, neuronal structure, network activity, and most importantly, memory formation). The rescue produced by increasing CREB was specific both anatomically and behaviorally and independent of plaque load or Aβ levels. Interestingly, humans with AD show poor spatial memory/navigation and AD brains have disrupted (1) CREB activation, and (2) spine density and dendritic complexity in hippocampal CA1 pyramidal neurons. These parallel findings not only confirm that TgCRND8 mice accurately model key aspects of human AD, but furthermore, suggest the intriguing possibility that targeting CREB may be a useful therapeutic strategy in treating humans with AD.
- Subjects :
- Alzheimer Disease pathology
Animals
CA1 Region, Hippocampal pathology
Cricetinae
Humans
Maze Learning physiology
Memory Disorders pathology
Memory Disorders prevention & control
Mesocricetus
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Transgenic
Alzheimer Disease metabolism
CA1 Region, Hippocampal metabolism
Cyclic AMP Response Element-Binding Protein physiology
Disease Models, Animal
Memory Disorders metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1740-634X
- Volume :
- 36
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21734652
- Full Text :
- https://doi.org/10.1038/npp.2011.107