The biochemical changes in hippocampal formation occurring in normal and seizure experiencing rats as a result of a ketogenic diet

Abstract

In this study, ketogenic diet-induced biochemical changes occurring in normal and epileptic hippocampal formations were compared. Four groups of rats were analyzed, namely seizure experiencing animals and normal rats previously fed with ketogenic (KSE and K groups respectively) or standard laboratory diet (NSE and N groups respectively). Synchrotron radiation based Fourier-transform infrared microspectroscopy was used for the analysis of distributions of the main organic components (proteins, lipids, compounds containing phosphate group(s)) and their structural modifications as well as anomalies in creatine accumulation with micrometer spatial resolution. Infrared spectra recorded in the molecular layers of the dentate gyrus (DG) areas of normal rats on a ketogenic diet (K) presented increased intensity of the 1740 cm(-1) absorption band. This originates from the stretching vibrations of carbonyl groups and probably reflects increased accumulation of ketone bodies occurring in animals on a high fat diet compared to those fed with a standard laboratory diet (N). The comparison of K and N groups showed, moreover, elevated ratios of absorbance at 1634 and 1658 cm(-1) for DG internal layers and increased accumulation of creatine deposits in sector 3 of the Ammon's horn (CA3) hippocampal area of ketogenic diet fed rats. In multiform and internal layers of CA3, seizure experiencing animals on ketogenic diet (KSE) presented a lower ratio of absorbance at 1634 and 1658 cm(-1) compared to rats on standard laboratory diet (NSE). Moreover, in some of the examined cellular layers, the increased intensity of the 2924 cm(-1) lipid band as well as the massifs of 2800-3000 cm(-1) and 1360-1480 cm(-1), was found in KSE compared to NSE animals. The intensity of the 1740 cm(-1) band was diminished in DG molecular layers of KSE rats. The ketogenic diet did not modify the seizure induced anomalies in the unsaturation level of lipids or the number of creatine deposits.

Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation

“…Such conclusion is also in agreement with our results. Our previous study showed that both KD1 and KD2 increased the level of ketone bodies in the hippocampal formation [21,22]. However, as it was shown in this paper only higher ketogenic ratio KD2 influenced the progress of pilocarpine evoked seizures and ameliorated the seizure behavior in animals.…”

“…Although, the content of PUFAs was slightly higher in KD1 comparing to KD2, lower ketogenic ratio KD did not induce significant changes in the unsaturation level of lipids within the hippocampal formation of normal rats [22]. From the other side, such effect was observed for animals treated with KD2 in which the content of unsaturated fatty acids was significantly higher comparing to rats on the standard diet [20].…”

“…Our previous studies carried out on different models of seizures showed that monitoring the hippocampal levels of Ca, Fe, Cu and Zn we can gain very important information about the pathogenesis and progress of epilepsy as well as about the neuroprotective and/or antiseizure action of particular drugs or diets [20][21][22][26][27][28][29][30]. Moreover, the existing evidence shows that the data on the elemental composition of this brain area can positively influence the research on the role of metals in the Alzheimer's disease or their use as contrast agents in magnetic resonance imaging [31][32][33].…”

“…The KDs with higher ketogenic ratios are usually more efficient in the seizure control but may be worse tolerate by the patients [19]. Our previous investigations showed, moreover, that elemental and biochemical changes occurring in the hippocampal formation after KD depended on its composition [20][21][22]. This suggests that also the mechanisms of anticonvulsive action of different KDs may not be the same.…”

The influence of the ketogenic diet on the elemental and biochemical compositions of the hippocampal formation

“…Examining seizure-induced elemental changes of the hippocampal formation, we were able to follow the processes of excitotoxicity and mossy fiber sprouting occurring in this brain area [18][19][20]. In turn, the use of FTIRM for biochemical analysis allowed us to detect the areas where abnormalities in the accumulation of main biomolecules (proteins, lipids, and compounds containing phosphate group(s)) and their structure (protein conformation and saturation and unsaturation levels of lipids) occurred [21,30].…”