engleski

The Effect of Olive Leaf Polyphenols on Altered Glutamate Homeostasis in the Rat Brain After Induced Experimental Autoimmune Encephalomyelitis (EAE)

Background: Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS) which allows rapid signal transmission in the synapse before its re-uptake into glia cells, particularly by astrocytes. High levels of extracellular glutamate are associated with excitotoxicity and disturbed glutamate transport, as found in some neurological disorders. We assume that glutamate excitotoxicity is linked with multiple sclerosis (MS). Methods: Experimental autoimmune encephalomyelitis (EAE) was used as an animal model of MS. Animals were divided into 2 major groups: one with and one without the olive leaf polyphenols (OLP) treatment. Before the initiation of clinical signs (i.e., on 8th day after EAE induction) the animals were treated with the olive leaf polyphenols (OLP) in the form of of olive leaf extract therapy (TOLE, i.p.) for 10 consecutive days, and sacrificed on the 20th or 30th day after EAE induction. In addition, OLP was used in the form of olive leaf infusion therapy (TOLI), given instead of drinking water, starting from EAE induction to the end of experiments, when the animals were sacrificed (20th and 30th days). The level of glutamate and activity of glutamate dehydrogenase (GLDH) were determined spectrophotometrically, the expression levels of glutamate dehydrogenase 1 (GLUD1), the astrocytic glutamate transporters glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) were determined by immunoblotting in the lysate of the cerebrum in the rat. Results: Increased glutamate level in the cerebrum, increased glutamate dehydrogenase activity, reduced expression level of glutamate dehydrogenase 1 and reduced glutamate transporter EAAT1 (GLAST) compared to the healthy control group were found in the EAE 20d group and the EAE 30d group. The expression of glutamate transporter EAAT2 (GLT-1) was unchanged in the group EAE 20d and 2.25 fold higher in the EAE 30d group compared the control group. It was shown that OLP decreased glutamate level, increased GLDH activity and increased expression level of GLUD1 (GLDH1) in the EAE 20d groups (TOLI and TOLE), as well as increased EAAT2 in the EAE 30d groups (TOLI and TOLE). Finally, the EAAT2/EAAT1 ratio significantly decreased in the EAE 30d groups (TOLI and TOLE).

Glutamate ; Brain ; Glutamate excitotoxicity ; Multiple sclerosis ; Experimental autoimmune encephalomyelitis (EAE) ; Glutamate dehydrogenase ; Glutamate transporters ; GLAST/EAAT1 ; GLT-1/EAAT2

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