Abstract

ABSTRACT

sphingosine-1 /sphingosine phosphokinase (SPHK/S1P) couple has a strong neuroprotective potential, particularly in the functioning of hippocampal neurons. Furthermore, it is established that diabetes is associated with cognitive decline, following damage to the nervous tissue. The aim of this work was to determine the involvement of the cerebral SPHK/S1P couple is involved in the maintenance of cognitive functions in rats in a model of diabetes induced by alloxan monohydrate. Materials and Methods: Male Wistar rats were used. They were divided into three groups (group 1: control, group 2: diabetics rats treated with distilled water and group 3: diabetics treated with D-erythro-dihydrosphingosine, a sphingosine phosphate inhibitor. Diabetes was induced by intraperitoneal injection of alloxan monohydrate at a single dose of 150 mg/kg. After confirmation of diabetes, the animals were treated with distilled water, for groups 1 and 2, and D-erythro-dihydrosphingosine (DEDHS) for group 3, for 28 days. Five days before the end of the treatments, working memory and spatial memory were tested in the object recognition and radial maze tests. The animals were then anesthetized and the hippocampus extracted from the brains. The S1P and SPHK content in the hippocampus was measured by mRNA amplification by polymerase chain reaction, after nucleic acid extraction. Results: Diabetes did not induce a significant alteration in the animals' preference for the novel object. However, inhibition of the SPHK/S1P pair led to a progressive decrease in the animals' preference for the novel object (p < 0.05). Furthermore, the number of errors made by the animals was significantly higher in the diabetic groups. Diabetes induced a depletion of the expression of the SPHK/S1P pair in the hippocampus of the animals. Conclusion: Our study showed that diabetes was associated with impaired working memory and a significant decrease in mRNA expression in the hippocampus of the animals. The SPHK/SP1 pair seems to be involved in neuroprotection against diabetes-associated cognitive impairment and provides insight into the underlying mechanism.