1: J Neurochem. 2003 Feb;84(3):417-31.

Meal size and frequency affect neuronal plasticity and vulnerability to disease:
cellular and molecular mechanisms.

Mattson MP, Duan W, Guo Z.

Laboratory of Neurosciences, National Institute on Aging, Gerontology Research
Center, Baltimore, Maryland 21224, USA.

Although all cells in the body require energy to survive and function properly,
excessive calorie intake over long time periods can compromise cell function and
promote disorders such as cardiovascular disease, type-2 diabetes and cancers.
Accordingly, dietary restriction (DR; either caloric restriction or intermittent
fasting, with maintained vitamin and mineral intake) can extend lifespan and can
increase disease resistance. Recent studies have shown that DR can have profound
effects on brain function and vulnerability to injury and disease. DR can protect
neurons against degeneration in animal models of Alzheimer's, Parkinson's and
Huntington's diseases and stroke. Moreover, DR can stimulate the production of
new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity,
which may increase the ability of the brain to resist aging and restore function
following injury. Interestingly, increasing the time interval between meals can
have beneficial effects on the brain and overall health of mice that are
independent of cumulative calorie intake. The beneficial effects of DR,
particularly those of intermittent fasting, appear to be the result of a cellular
stress response that stimulates the production of proteins that enhance neuronal
plasticity and resistance to oxidative and metabolic insults; they include
neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein
chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins.
Some beneficial effects of DR can be achieved by administering hormones that
suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing
the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic.
The profound influences of the quantity and timing of food intake on neuronal
function and vulnerability to disease have revealed novel molecular and cellular
mechanisms whereby diet affects the nervous system, and are leading to novel
preventative and therapeutic approaches for neurodegenerative disorders.

PMID: 12558961 [PubMed - indexed for MEDLINE]