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NIA researchers find protein PGC-1alpha may play important role in brain health

The human brain is made up of tens of billions of neurons, brain cells that act as information messengers, transmitting and receiving chemical and electrical signals. These messages are received by branch-like cell structures called dendrites after traveling across synapses, the tiny gap between neurons. Now, researchers in NIA’s Intramural Research Program have shown in mice that a protein, PGC-1alpha, may play an important role in forming and maintaining healthy dendrites and synapses in the hippocampus--the brain region important to learning and memory. The findings are reported online in the Dec. 4, 2012, issue of Nature Communications.

PGC-1alpha protein acts by stimulating the proliferation of mitochondria, the “powerhouses” of the cell that generate energy needed for the cell to function and survive. In cultured rat hippocampal neurons, the process resulted in increased numbers of dendrite spines; knocking out the protein not only reduced the number but also the thickness of the spines. The NIA investigators also found that brain-derived neurotrophic factor (BDNF), which is involved in learning and memory and may protect neurons against degeneration, stimulated the production of PGC-1alpha and mitochondrial activity in adult mice.

Because BDNF is believed to play a key role in beneficial effects of exercise and cognitive stimulation on brain health, this suggests a role for PGC-1alpha and mitochondria in healthy brain function. Further study is needed to determine if PGC-1alpha may be a promising therapeutic target for Alzheimer’s disease and other neurodegenerative disorders.

Reference: Cheng, A. et al. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines. Nature Communications 3:1250. doi:10.1038/ncomms2238 2012