CR ± ketogenic diet for brain

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Hi All,

For:

Cheng CM, Hicks K, Wang J, Eagles DA, Bondy CA.

Caloric restriction augments brain glutamic acid decarboxylase-65 and -67

expression.

J Neurosci Res. 2004 Jul 15;77(2):270-6.

PMID: 15211593

Details from the available pdf may offer interest.

“IGF receptor and GLUT3 expression were significantly reduced by the

calorie-restricted, standard chow diet but significantly increased with the

calorie-restricted, ketogenic diet”?

Glucose was certainly lower with the ketogenic CR compared with the standard CR,

but

the ketones were at relatively huge levels.

Body weights were over 50% lower for 10% CR?

The role of CR of brain glutamic acid decarboxylase-65 and –67 in other brain

diseases seems to be of interest.

Abstract

The ketogenic diet is a very low-carbohydrate, high-fat diet used to treat

refractory epilepsy. We hypothesized that this diet may act by increasing

expression

of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in

gamma-aminobutyric

acid (GABA) synthesis. Thus, we evaluated brain GAD levels in a

well-established,

seizure-suppressing, rodent model of the ketogenic diet. Because the diet is

most

effective when administered with a modest (10%) calorie restriction, we studied

three groups of animals: rats fed ad libitum standard rat chow (Ad lib-Std);

calorie-restricted standard chow (CR-Std); and an isocaloric, calorie-restricted

ketogenic diet (CR-Ket). We found that GAD67 mRNA was significantly increased in

the

inferior and superior colliculi and cerebellar cortex in both CR diet groups

compared with control (e.g., by 45% in the superior colliculus and by 71% in the

cerebellar cortex; P < .001). GAD65 mRNA was selectively increased in the

superior

colliculus and temporal cortex in both CR-Std and CR-Ket diet groups compared

with

ad lib controls. The only apparent CR-Ket-specific effect was a 30% increase in

GAD67 mRNA in the striatum (P = .03). Enhanced GAD immunoreactivity was detected

in

parallel with the mRNA changes. These data clearly show that calorie restriction

increases brain GAD65 and -67 expression in several brain regions, independent

of

ketogenic effects. These observations may explain why caloric restriction

improves

the efficacy of the ketogenic diet in treating epilepsy and suggest that diet

modification might be useful in treatment of a number of brain disorders

characterized by impaired GAD or GABA activity.

Table I. Effects of Diets on Body and Brain Weights, Serum Glucose, and Ketone

Levels

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

Ad lib-Std CR-Std Percentage of control CR-Ket Percentage of control

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

Body weight (g) 85.3±3.0 41.7±2.1* - 51% 42.5±3.8* -51%

Brain weight (mg) 1.4±0.05 1.25±0.03* -10% 1.27±0.02* -10%

Glucose (mg/dl) 179±10.5 127±15.9* -29% 57.5±7.2** -68%

Ketones (mM) 0.27±0.001 0.23±0.03 No change 4.4±0.67** +1530%

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

The data represent means±SEM for six animals per group.

* P < .01 compared with AL-Std.

** P < .0001 compared with AL-Std and CR-Std.

Table II. Comparison of GAD67 and GAD65 mRNA Levels in Specific Brain Regions of

Different Diet Groups

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

Brain region CR-Ket vs Ad lib-Std (%) P value CR-Std vs Ad lib-Std (%) P value

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

GAD67

Inferior colliculus 148.8±17.1 .009* 141.9±7.4 .021*

Superior colliculus 146.2±5.0 .0001* 145.5±8.8 <.0001*

Frontal cortex 119.3±10.1 .331 125.6±17.8 .203

Temporal cortex 127.9±15.0 .177 129.0±13.8 .160

Striatum 130.3±8.1 .032* 112.2±12.5 .358

Cerebellum 139.7±12.1 .019* 171.0±12.3 .0003*

GAD65

Inferior colliculus 95.1±7.0 .663 101.2±13.1 .917

Superior colliculus 119.9±5.9 .008* 119.2±4.0 .014*

Frontal cortex 100.1±11.3 .992 112.9±4.3 .332

Temporal cortex 146.3±19.0 .038* 151.7±15.8 .029*

Striatum 92.2±5.7 .357 89.0±7.6 .220

Cerebellum 82.9±7.2 .209 100.8±11.7 .951

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

Data are expressed as percentage of Ad lib-Std control (N = 6 per group). The

quantification of hybridization signal was detailed in Materials and Methods.

* Statistically significant difference was obtained by comparing different

diet to

Ad Lib-Std control by ANOVA, followed by Fisher's least significant difference

tests.

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

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