Biology clock, CR and brain function

[Guest guest]

The below paper has what to me seems to be some information of interest and this

information extends beyond the information in the abstract provided by Medline.

The

journal is a neuroscience journal of high repute, and the neuroscience topic

predominates.

That the abstract reports that CR caused a " marked preprandial rise in locomotor

activity, body temperature and wakefulness " was what may be the information of

most

significance for those of us who are not neuroscientists.

The information in Table 1 informed. In addition to what information was in the

abstract, however, the total daily exercise was less with CR, so the expectation

of

food seems to cause excitement, some might say agitation, above a lower

baseline.

The percentage differential between day- and nighttime exercise levels favored

the

daytime for the CRers, relative to the ad libitum fed rats. How much the CRer

relative to ad libitum eating rat body temperatures rose just before eating

relative

to the daily body temperature fluctuations was highly significant. The almost

10-fold greater differential between the daily low body temperature and and the

before-mealtime body temperature with CR versus ad libitum eating was

substantial.

The internal biochemistry effects may be greater than the apparent effect (that

is,

exercise level) of the expectation of receiving the next meal for CRers relative

to

ad libitum eaters.

Call me ignorant, but I had not idea on what acrophase meant until finding:

acro- Combining form meaning: 1. Extremity, tip, end, peak, topmost. 2. Extreme.

Origin: G. Akron, highest point, extremity; akros, topmost, outermost, inmost,

extreme, tip.

Wikipedia gives only: http://en.wikipedia.org/wiki/Acro.

The acrophase was about midway between the waking time and sleep time with ad

libitum fed rats, but was approximately the same number of hours from the

feeding

time for the CRer rats.

The CR rats spent relative to ad libitum fed rats much more time awake before

their

meals (in strong anticipation of feeding). The CRers also spent more daylight

hours

awake than the ad libitum fed rats.

For Table 2, the information may interest neuroscientists . The acronyms seem

to be

D for dorsomedial, V for ventricular, L for lateral, P for parventicular, H for

hypothalamic and A for area. The neuroanatomy of the region was examined for

its

functions in the effects of CR.

I hope that my interpretation serves to highlight important data in the full

text

and does not present the findings in error, such as stating the opposite of the

actual information in the paper, as I have frequently been reminded of and found

to

occur after rereading the message when it has been sent.

I hope that there are not too many errors in the transfer of information and the

manual insertion of all the ± and × symbols that the HTML text omitted. The

information could not be transferred from the available pdf.

Gooley JJ, Schomer A, Saper CB.

The dorsomedial hypothalamic nucleus is critical for the expression of

food-entrainable circadian rhythms.

Nat Neurosci. 2006 Feb 19; [Epub ahead of print]

PMID: 16491082

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16491082 & query_hl=1 & itool=pubmed_docsum

.... Adult male Sprague-Dawley rats (275–325 g, Harlan) ... 12:12 light-dark

cycle

(lights on at 7:00 a.m., 100 lux). During periods of food availability, rats

were

fed Purina Rat Chow (Purina #5053, 20% protein, 4.5% fat, 6% fiber) ...

restricted

feeding for 2 weeks with a daily 4-h meal presented at midday (1:00 p.m.). The

control group (n = 24) continued to have free access to food for the next 2

weeks

....

Circadian rhythms of behavior and physiology can be entrained by daily cycles of

restricted food availability, but the pathways that mediate food entrainment are

unknown. The dorsomedial hypothalamic nucleus (DMH) is critical for the

expression

of circadian rhythms and receives input from systems that monitor food

availability.

Here we report that restricted feeding synchronized the daily rhythm of DMH

activity

in rats such that c-Fos expression in the DMH was highest at scheduled mealtime.

During food restriction, unlesioned rats showed a marked preprandial rise in

locomotor activity, body temperature and wakefulness, and these responses were

blocked by cell-specific lesions in the DMH. Furthermore, the degree of food

entrainment correlated with the number of remaining DMH neurons, and lesions in

cell

groups surrounding the DMH did not block entrainment by food. These results

establish that the neurons of the DMH have a critical role in the expression of

food-entrainable circadian rhythms.

Table 1 Comparison of behavior and physiology in unlesioned and DMH-lesioned

rats

during ad lib feeding and restricted feeding

=====================================================

Measurement Feeding Unlesioned DMH Lesions t-test, P value

=====================================================

Daily locomotor activity counts

ad lib 927.0±76.7 469.1±48.8 1.5×10-4

restricted 635.2±49.7 417.6±44.2 4.5×10-3

t-test, P value 3.8×10-4 0.023

Preprandial locomotor activity counts (10:00 a.m. to 1:00 p.m.)

ad lib 43.4±5.2 32.9±4.6 0.15

restricted 74.1±6.7 40.8±5.9 3.5×10-3

t-test, P value 5.2×10-5 0.050 1.7×10-3

Percent daily locomotor activity occurring during daytime

ad lib 32.3±1.8 36.8±1.5 0.074

restricted 65.1±2.2 44.5±2.3 6.0×10-6

T-test, P value 3.6×10-6 6.4×10-3

Mean daily body temperature

ad lib 37.50±0.039 37.26±0.031 1.9×10-4

restricted 37.07±0.040 36.97±0.030 0.054

t-test, P value 3.1×10-6 1.0×10-6

Body temperature rhythm magnitude (peak minus trough)

ad lib 1.24±0.064 1.33±0.067 0.34

restricted 1.66±0.060 1.67±0.070 0.92

t-test, P value 1.3×10-3 2.0×10-3

Preprandial body temperature magnitude, °C above the nadir

ad lib 0.064±0.017 0.078±0.023 0.648

restricted 0.62±0.043 0.032±0.022 2.3×10-7

t-test, P value 1.4×10-6 0.21

Body temperature rhythm acrophase

ad lib 12:01a.m.±0:10 12:47a.m.±0:09 4.4×10-3

restricted 7:25p.m.±0:08 11:28p.m.±0:14 3.7×10-9

t-test, P value 5.6×10-10 2.9×10-9

Daily wakefulness (min)

ad lib 684.8±20.5 672.3±19.7 0.67

restricted 685.6±17.2 629.2±27.3 0.13

t-test, P value 0.97 0.23

Preprandial wakefulness (min; 10:00 a.m. to 1:00 p.m.)

ad lib 39.9±3.2 59.5±2.2 1.4×10-3

restricted 101.6±4.5 70.3±5.6 2.7×10-3

t-test, P value 1.7×10-4 0.085

Percent daily wakefulness occurring during daytime

ad lib 31.2±0.76 41.8±0.47 1.0×10-5

restricted 52.1±1.6 40.9±1.9 2.3×10-3

t-test, P value 5.7×10-4 0.66

Rat chow consumed (g)

ad lib 22.2±0.57 19.0±0.91 0.019

restricted 15.9±0.56 15.5±0.73 0.70

t-test, P value 1.9×10-5 0.14

=====================================================

Locomotor activity and body temperature in each unlesioned (n=10) and

DMH-lesioned

(n=9) rat was averaged over the final 2 weeks of ad lib feeding and compared to

the

final 2 weeks of restricted feeding. Similarly, wakefulness in each unlesioned

(n=5)

and DMH-lesioned (n=5) rat was averaged over the final 3 d of ad lib feeding and

compared to the final 3 d of restricted feeding. To measure the body temperature

rhythm acrophase during restricted feeding, the daily meal was omitted for 2 d

to

unmask the thermogenic effects of feeding on body temperature. Likewise, percent

daily locomotor activity and wakefulness occurring during the daytime in the

restricted feeding condition were measured during the subsequent food

deprivation

period. The mean±s.e.m. is shown for each group of unlesioned and DMH-lesioned

rats.

Table 2 Comparison of food entrainment in unlesioned rats, DMH-lesioned rats and

control-lesioned rats

=====================================================

Measurement Unlesioned DMH-X DHA-X VMHdm-X LHA-X PH-X

=====================================================

Rats 10 9 3 6 4 4

Remaining DMH neurons 100±4.2 10.5±2.5 78.3±5.6 74.8±3.4 84.2±1.7 85.9±3.9

Food anticipatory activity 100±12.0 26.5±5.5 93.3±9.6 57.9±16.5 143.2±16.7

77.7±30.7

Preprandial body temperature 100±7.0 5.1±3.5 100.9±5.0 96.0±14.5 112.4±8.9

88.3±19.0

Phase shift in body temperature 100±3.7 28.3±4.3 78.0±15.8 68.8±19.2 99.5±4.2

100.9±0.9

ioned and DMH-lesioned rats during ad lib feeding and restricted feeding

=====================================================

Lesions in the DMH, but not in surrounding brain nuclei, caused profound

deficits in

food entrainment. DMH lesions were defined by >75% cell loss in the DMH, and

lesions

resulting in greater than one-third cell loss in the DMH were omitted from each

group of control lesions. The mean±s.e.m. is shown for each group of lesioned

rats.

The magnitude of food entrainment in each group was roughly proportional to the

remaining number of DMH neurons. For ease of comparison, all values are scaled

to

100 for unlesioned rats. Control lesions in the VMHdm were defined by >75% cell

loss

in the VMHdm.

-- Al Pater, alpater@...

-- Al Pater, PhD; email: old542000@...

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