The Beneficial Effects of Dietary Restriction on Learning are Distinct from its Effects on

Longevity and Mediated by Depletion of a Neuroinhibitory Metabolite

Introduction

Dietary restrictions (DR), specifically ones that inhibit insulin signaling, have a

known connection to longevity in mammals due to improving molecular function in

cells. The same dietary restrictions have an implied effect on learning and memory as

well, but it is not clear whether these improved cognitive abilities are a byproduct of the

longevity and maintenance of neurons or if it is due to a direct effect on cellular

mechanisms from the reduction of insulin signaling.

The researchers here try to distinguish whether improved cognitive abilities

happen as a direct consequence of DR, or if it is simply a result of the wide range of

beneficial effects on organismal activities that comes from enhanced longevity. This

information could help researchers study degenerative brain diseases in the real world

such as Alzheimers.

Materials and Methods

All experiments were done on Caenorhabditis elegans (C. elegans) grown in 15-

ml cultures. C. elegans have shown the same effects in both learning improvement and

longevity as in humans when placed under conditions which reduce insulin signaling. C.

elegans have been used in studies related to human longevity and learning before

because many of the molecular components necessary for learning in humans have

been preserved through evolution in C. elegans.

 To test the short term learning abilities of the animals researchers performed an

associative learning assay on the animals using butanone. Butanone on its own has a

mildly attractive odor, but researchers placed butanone exclusively with food for the

variable groups of C. elegans until they became attracted to butanone on its own. This

assay provided a way to observe the short term learning abilities in the experiments

animals under different conditions all aimed to improve learning and memory: genetic

intervention (done using plasmids to extract different gene expressions), reduction in

insulin signaling through dietary restriction (long and short periods of fasting before

exposure to butonane), and pharmacological intervention.

Researchers then used metablolite extraction and metabolite determination to

evaluate what metabolic factors were causing improved learning in different C. elegans.

Lifespan was also being monitored to see if the improved cognitive abilities in this

experiement were in fact resulting just from longevity.

C. elegans were studied using confocal microscopy by being immobilized in 2%

agaraose pads containing NaN3 and using a 60X objective on a Nikon C1si point

scanning confocal microscope.

Results

Both chronic and acute dietary restriction showed an enhancement in the C.

elgans learned attraction to butonane, with longer fasting showing greater results (up

to one hour fasting before exposure to butonane with no added improvement

thereafter).
The genetic and pharmalogical manipulations that were meant to mimic the effects of

DR also showed enhanced learning capacities in the C. elegans. The lifespan of the

studied C. elegans were not above average showing that while this experiment did have

an effect on cognitive abilities it had no relation to longevity.

Discussion

All of the improved effects on learning from DR, genetic manipulation, and

pharmological intervention showed an important link to kynurenic acid (KYNA) and

glutamate receprots called N-methyl D-aspartates (NMDARs) within neurons. NMDARs

are critical for learning in mammals, and KYNA is a local competitor, which antagonizes

these crucial receptors causing a decrease in learning abilities. What DR and its genetic

and pharmological mimetics did was decrease levels of KYNA in specific neurons so that

the NMDAR receptors could function optimally leading to increased learning capacity.

While different levels of KYNA had clear effects on cognitive improvement it showed

effect on lifespan of the C. elegans. This information answers the question that the

researchers sought out: DR has a direct impact on learning abilities in mammals and is

not a by product of longevity.

 Reflection

Not only did I learn about the outcomes of this specific experiment while writing

my summary, I learned how to read and understand scientific writing. I was able to see

how research results are written into specific categories and the details in which

researchers describe their experiments including all of the factors that go into

conducting an error proof experiment.

I improved my communication skills by translating a fairly hard to read research

paper into an easier to understand summary. This required me to take the time to fully

understand what I was reading to the best of my ability so that I could condense my

reading into an understandable summary.

Reading this research paper improved my critical thinking by showing me all of

the different factors that had to go into consideration when conducting the experiment.

There are many variables that I never would have thought of that could greatly affect

the outcome of the experiment. As a result I will try to think outside of the limitations of

my experiences.