Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2011 Oct 5;31(40):14361-6.
doi: 10.1523/JNEUROSCI.3171-11.2011.

Metabolic Dysfunction Associated With Adiponectin Deficiency Enhances Kainic Acid-Induced Seizure Severity

Affiliations
Free PMC article
Comparative Study

Metabolic Dysfunction Associated With Adiponectin Deficiency Enhances Kainic Acid-Induced Seizure Severity

Edward B Lee et al. J Neurosci. .
Free PMC article

Abstract

Metabolic syndrome has deleterious effects on the CNS, and recent evidence suggests that obesity rates are higher at presentation in children who develop epilepsy. Adiponectin is secreted by adipose tissue and acts in the brain and peripheral organs to regulate glucose and lipid metabolism. Adiponectin deficiency predisposes toward metabolic syndrome, characterized by obesity, insulin resistance, impaired glucose tolerance, hyperlipidemia, and cardiovascular morbidity. To investigate the relationship between metabolic syndrome and seizures, wild-type C57BL/6J and adiponectin knock-out mice were fed a high-fat diet, followed by treatment with low doses of kainic acid to induce seizures. Adiponectin deficiency in mice fed a high-fat diet resulted in greater fat accumulation, impaired glucose tolerance, hyperlipidemia, increased seizure severity, and increased hippocampal pathology. In contrast, there were no adverse effects of adiponectin deficiency on metabolic phenotype or seizure activity in mice fed a normal (low-fat) chow diet. These findings demonstrate that metabolic syndrome modulates the outcome of seizures and brain injury.

Figures

Figure 1.
Figure 1.
Effects of HFD on body composition and glucose tolerance. A, ADP-KO and WT mice fed HFD were assessed for body weight, fat content and lean mass, shown as mean ± SE (n = 10 per group). **p < 0.01; ***p < 0.001. B, Blood glucose measurements before and after a glucose challenge are shown as mean ± SE (n = 9–10 per group; genotype p = 0.0164, time p < 0.0001, interaction p = 0.281). Post hoc analysis revealed significantly differences at times 0 (p = 0.049), 60 min (p = 0.0213) and 120 min (p = 0.0135).
Figure 2.
Figure 2.
Kainic acid seizure in mice fed HFD. A, Data are mean ± SE; n = 6. ADP-KO mice exhibited higher seizure scores (genotype p = 0.0127, time p < 0.0001, interaction p < 0.0001). Post hoc analysis with Bonferroni's correction revealed higher seizure scores from 60 min to 105 min (p < 0.01 to p < 0.001). B, Brain sections were stained with cresyl violet (top), or for GFAP (middle), and Iba1 (bottom). Representative images of hippocampus are shown, with higher-power images of the dentate gyrus endplate shown in the insets. Hippocampal regions are labeled for reference. Scale bars: Top and middle, 500 μm; bottom, 100 μm; inset, 50 μm. C, Semiquantitative pathology scores, shown as mean ± SE; n = 6. Dashed line denotes baseline normal score of 1 (**p < 0.01, ***p < 0.001). D, Neurodegeneration and gliosis in a kainic acid-treated ADP-KO mouse. Cresyl violet (left and middle)- and Iba1 (right)-stained sections are shown. Boxed region is CA1. Arrowhead points to a pyknotic neuron in contrast with viable neuron (asterisk). Scale bars: left, 500 μm; middle, 50 μm; right, 100 μm.
Figure 3.
Figure 3.
Intrahippocampal kainic acid and seizure-related pathology. A, Hippocampal sections were stained with cresyl violet (top, at low and high magnification), or for GFAP (middle, at low and high magnification), Iba1 (middle, at low magnification), and synaptophysin (SYN; bottom, at high magnification). Scale bars: lower-magnification panels, 500 μm; higher-magnification panels, 50 μm. DG, Dentate gyrus; CA3, cornu ammonis 3; H, hilum. B, Dentate gyrus thickness measurements shown as mean ± SE with dashed line denoting normal thickness. C–E, Semiquantitative pathology scores, shown as mean ± SE; n = 4–6. Dashed line denotes normal baseline score of 1. *p < 0.05 for genotype by two-way ANOVA).

Similar articles

See all similar articles

Cited by 9 articles

See all "Cited by" articles

Publication types

Feedback