Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Aβ and tau pathologies in 3xTg-AD mice
Abstract
In addition to the occurrence of numerous neurofibrillary tangles and Aβ plaques, neurogenesis and neuronal plasticity are markedly altered in Alzheimer disease (AD). Although the most popular therapeutic approach has been to inhibit neurodegeneration, another is to promote neurogenesis and neuronal plasticity by utilizing the regenerative capacity of the brain. Here we show that, in a transgenic mouse model of AD, 3xTg-AD mice, there was a marked deficit in neurogenesis and neuroplasticity, which occurred before the formation of any neurofibrillary tangles or Aβ plaques and was associated with cognitive impairment. Furthermore, peripheral administration of Peptide 6, an 11-mer, which makes an active region of ciliary neurotrophic factor (CNTF, amino acid residues 146-156), restored cognition by enhancing neurogenesis and neuronal plasticity in these mice. Although this treatment had no detectable effect on Aβ and tau pathologies in 9-month animals, it enhanced neurogenesis in dentate gyrus, reduced ectopic birth in the granular cell layer, and increased neuronal plasticity in the hippocampus and cerebral cortex. These findings, for the first time, demonstrate the possibility of therapeutic treatment of AD and related disorders by peripheral administration of a peptide corresponding to a biologically active region of CNTF.
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Associated with decreased synaptic efficacy is a decline in brain levels of synaptophysin, suggesting an actual loss of synapses.
“Associated with this decreased synaptic efficacy is a decline in brain levels of the ubiquitous presynaptic marker synaptophysin, suggesting an actual loss of synapses (Blanchard et al., 2010).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Blanchard et al., 2010
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Tau pathology and neurodegeneration
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- Authors
- Blanchard, J., Wanka, L., Tung, Y.-C., Cárdenas-Aguayo, M. D. C., LaFerla, F. M., Iqbal, K., & Grundke-Iqbal, I.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- University of California, Irvine (US)
- Venue
- Acta Neuropathologica
- Published
- 2010-08-10
- Volume
- 120
- Issue
- 5
- Pages
- 605-621
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2026816538
- Cited by
- 85
- References
- 8
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 6 · 2012: 5
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office for People With Developmental Disabilities
- T.L.L Temple Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, 3xTg-AD mice, neurogenesis, neuroplasticity, cognitive impairment, ciliary neurotrophic factor, dentate gyrus, hippocampus, cerebral cortex, neurofibrillary tangles, amyloid plaques, tau pathology
- MeSH terms
- Alzheimer Disease, Animals, Brain, Chromatography, High Pressure Liquid, Cognition Disorders, Disease Models, Animal, Immunohistochemistry, Memory, Mice, Transgenic, Neuronal Plasticity, Peptides, Blotting, Western, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Protein Structure, Secondary, Neuroprotective Agents, Maze Learning, Ciliary Neurotrophic Factor, Mice, Neurogenesis, Plaque, Amyloid
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