Low glycemic index diet restrains epileptogenesis in a gender specific fashion
Authors:
Caterina Michetti (1,2), Daniele Ferrante (1), Barbara Parisi (1), Lorenzo Ciano (2), Cosimo Prestigio (1), Silvia Casagrande (1), Sergio Martinoia (1), Enrico Millo (1), Pierluigi Valente (1,3), Silvia Giovedi (1,3), Fabio Benfenati (2,3), Pietro Baldelli (1,3)
Organisations:
1: Department of Experimental Medicine, University of Genova
2: Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia
3: IRCCS, Ospedale Policlinico San Martino, Genova
Presenting author:
Caterina Michetti
Exposition date:
Friday, September 15, 2023
Exposition position:
069/1
Dietary restriction, such as low glycemic index diet (LGID), have been extensively and successfully used as antiepileptic approach; however, if such diet could also exert a real antiepileptogenic action is still unclear. Here, we investigated in Synapsin (Syn) II KO mice, a mouse model of hereditary temporal lobe epilepsy, whether administration of LGID during the latent period, which precedes the appearance of the first seizure, inhibits epileptogenesis.
In these mice, seizures appear around 3 months after birth, offering a window of opportunity in which LGID may affect the epileptogenic process. Pregnant Syn II KO mice were fed either a LGID or standard diet (StD) during gestation and lactation. Both diets were maintained in weaned mice up to 5 months of age. The latency and duration of the first behavioral seizure, as well as the behavioral analyses of the seizure elements were investigated by video recordings. Notably, LGID delayed the seizure onset and induced a reduction of seizures severity only in Syn II KO female mice. Behavioral seizure analysis was followed by high-density multielectrode array recordings in acute brain slices. Coherently with the behavioral results, a reduction of the frequency, amplitude, duration, covered-area and velocity of propagation of inter-ictal events was observed in the hippocampus of LGID-fed Syn II KO females, but not in males, suggesting a possible involvement of sexual hormones in this gender-specific effect of LGID. ELISA-based analysis of plasmatic and cortical ALLO revealed did not show any gender-influence. Notably, LGID increased cortical but not plasmatic concentrations of ALLO in female, while it remained unchanged in male mice.
These results strongly suggest that the gender-specific interference with the epileptogenic process induced by LGID finds a fundament in a gender-specific increase of cortical ALLO, a neurosteroid known for its capability to strength GABAergic inhibitory inputs, acting as an endogenous benzodiazepine.
