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Chronic agomelatine treatment suppresses the kainate-induced glial reaction during epileptogenesis in rats

N. Lazarov, J. Tchekalarova, D. Atanasova

Abstract

Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. The aim of this study was to examine the effect of the novel antidepressant agomelatine (Ago), a po­tent melatonin MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist, on glial activity during kainate (KA)-induced epileptogenesis.

Brain sections were immunostained with the microglial marker Iba-1 and two astrocyte-specific markers, GFAP and S100 beta, and the glial cell morphology in brain structures vulnerable to KA-induced neurotoxicity was de­scribed in the KA-treated groups and their matched controls, respectively.

Both control and Ago-treated groups were characterized with ramified microglial cells with fine processes. After administration of KA, activated Iba-1-immunoreactive microglial cells in the dorsal and ventral hippocampus, dentate gyrus, as well as in the basolateral amygdala (BLA) and piriform cortex were increased in number and displayed enlarged round-shaped bodies and arborization. Chronic Ago treatment during epileptogenesis sig­nificantly diminished their number compared to that in the matched vehicle-treated epileptic group, specifical­ly in the CA1a, CA1b, CA1c and CA3c subfields of dorsal hippocampus, BLA and piriform cortex. Conversely, the KA-induced reactive astrogliosis was more restricted and both GFAP- and S100 beta-immunostained cells were observed mainly in the CA1 and CA3c fields of dorsal hippocampus and piriform cortex. The Ago treatment did not significantly reduce the number of immunopositive astrocytes in the CA2, CA3a, CA3b subfields of the dor­ sal and CA1, CA2, CA3 subfields of the ventral hippocampus, the dentate gyrus and the BLA. In addition, only a few immunostained ramified astrocytes were scattered in the ventral hippocampus of the KA-veh group, while the Ago-treated group showed a considerable increase of immunoreactive cells in this area compared to controls.

The present results show that chronic Ago treatment during epileptogenesis prevents the KA-induced microglial activation and suppresses the neuronal cell death in the vulnerable limbic regions. It can provide effective ther­apy for brain disorders involving neuronal damage, neuroinflammation and oxidative stress such as epilepsy.





DOI: http://dx.doi.org/10.14748/ssm.v49i0.4810

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About The Authors

N. Lazarov
Medical University of Sofia
Bulgaria

J. Tchekalarova
Medical University of Sofia
Bulgaria

D. Atanasova
Medical University of Sofia
Bulgaria

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