Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease

By A. Nagahara, D. Merrill, G. Coppola, Shingo Tsukada, B. E. Schroeder, G. Shaked, Ling Wang, A. Blesch, A. Kim, J. Conner and 7 more. Nature Medicine, 2009

1,007 citations recorded by the source corpus.

Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer's disease. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer's disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes aberrant gene expression, improves cell signaling and restores learning and memory. These outcomes occur independently of effects on amyloid plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves age-related perturbations in gene expression and restores cell signaling. In adult rats and primates, BDNF prevents lesion-induced death of entorhinal cortical neurons. In aged primates, BDNF reverses neuronal atrophy and ameliorates age-related cognitive impairment. Collectively, these findings indicate that BDNF exerts substantial protective effects on crucial neuronal circuitry involved in Alzheimer's disease, acting through amyloid-independent mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy for Alzheimer's disease.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Physiology

View Paper: https://www.semanticscholar.org/paper/927ffcf0d1fefa93b088dd0aaac12a1fbdc3b465

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Physiology

Citations in the corpus

Amyloid Precursor Protein Processing and Alzheimer’s Disease (2011, background): “First, the levels of brain-derived neurotrophic factor (BDNF) in the brains of patients with AD decrease (Lee et al. 2005, Peng et al. 2005), and BDNF infusion can improve cognitive function in aged primates (Nagahara et al. 2009).”
Potential therapeutic uses of BDNF in neurological and psychiatric disorders (2011, background): “Therapeutic effects of BDNF In addition to their major roles in supporting neuronal survival and function during development and in adulthood, nervous system growth factors exert potent pro-survival and functional effects in models of neurological disease (for example, striking effects hav”
Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain (2019, background): “In a recent study, delivery of BDNF to the entorhinal cortex in amyloid transgenic mice reversed neuronal atrophy and synaptic loss, regulated neuronal signaling, and diminished the related mnemonic deficits without changes in the amyloid plaque load (Nagahara et al., 2009) indicating that BDNF can ”
A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease (2010, background): “Recent work suggests that enhancing the delivery of the neurotrophin brain-derived neurotrophic factor in animal models of AD may reverse synaptic loss and improve cognitive function.(63) Whether DBS regulates neurotrophin expression and neurogenesis in humans and whether this occurs in the diseased”
Post-synaptic BDNF-TrkB Signaling in Synapse Maturation, Plasticity and Disease (2010, background): “Diseases associated with some perturbation of BDNF signaling are diverse: epilepsy (He et al., 2004); mood disorders (Neves-Pereira et al., 2002; Sklar et al., 2002; Schumacher et al., 2005; Strauss et al., 2005), neurodegenerative diseases such Huntington's Disease (Zuccato et al., 2001; Zuccato et”
Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease (2009, background): “Taken together our findings indicate the potent effect neurotrophins have on brain function despite rampant pathology and suggest that the further development of cell-based therapies or other methods that modulate neurotrophin levels could provide a viable approach to treat AD (33).”
The Diabetes Drug Liraglutide Prevents Degenerative Processes in a Mouse Model of Alzheimer's Disease (2011, background): “…neurotrophic factor (BDNF) injected intracerebroventricularly led to an enhancement in hippocampal synaptic density (Blurton-Jones et al., 2009), while gene delivery of BDNF in rodents and primates improved cognition and synaptic signaling (Nagahara et al., 2009), without altering plaque load.”
GDNF, NGF and BDNF as therapeutic options for neurodegeneration. (2013, background): “proved spatial learning and memory in water maze performance (Nagahara et al., 2009).”