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]