The effects of AGRP neurons in the arcuate nucleus on kainic acid-induced epilepsy

The modulatory effect of Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus with gamma aminobutyric acid (GABA) is important for energy metabolism. It is known that energy metabolism is impaired in epilepsy. Due to the anticonvulsant effects of GABA and neuropeptide Y associated with AgRP neurons, it was hypothesized that these neurons may play a role in epilepsy. We presumed that acute and chronic stimulation of AgRP neurons may affect kainic acid (KA)-induced experimental epilepsy model. Thirty female and male transgenic AgRP-cre mice were used. Epileptic activity was induced with 100 nl of KA (15mM, in saline). Optogenetic and chemogenetic methods were used to investigate the effects of acute and chronic stimulation of AgRP neurons on epileptic activity. As a result, the control and epilepsy groups were compared according to electroencephalography (EEG), cell attach recording, feeding behaviour, open field, object location and novel object recognition tests. All experiments were approved by the local animal research ethics committee. One-Way-ANOVA and Student-t-test were applied for statistical analysis. Seizures were scored according to the racine scale. Three and above were considered as seizures and compared with the control group (p<0.05). Although the epilepsy and control groups continued in the same pattern in EEG, the epilepsy group followed a higher numeric trend in amplitude. During the open field test, it was observed that the epilepsy group, whose AgRP neurons were chronically stimulated, spent less time in the inner zone compared to the control group (p<0.05). Even though the acute and chronic stimulation of AgRP neurons did not make a significant difference in the epilepsy group, it was observed that the results followed a similar trend to the control group. Our findings suggest that AgRP neurons may have a modulatory effect in epilepsy.