Insulin decreases epileptiform activity in rat layer 5/6 prefrontal cortex in vitro
Por:
Villalobos, N., Ramirez-Sanchez, E., Mondragon-Garcia, A., Garduño J., Castillo-Rolon, D., Trujeque-Ramos, S., Hernandez-Lopez, S.
Ahead of Print:
1 feb 2023
Resumen:
Accumulating evidence indicates that insulin-mediated signaling in the
brain may play important roles in regulating neuronal function.
Alterations to insulin signaling are associated with the development of
neurological disorders including Alzheimer's disease and Parkinson's
disease. Also, hyperglycemia and insulin resistance have been associated
with seizure activity and brain injury. In recent work, we found that
insulin increased inhibitory GABA(A)-mediated tonic currents in the
prefrontal cortex (PFC). In this work, we used local field potential
recordings and calcium imaging to investigate the effect of insulin on
seizure-like activity in PFC slices. Seizure-like events (SLEs) were
induced by perfusing the slices with magnesium-free artificial
cerebrospinal fluid (ACSF) containing the proconvulsive compound
4-aminopyridine (4-AP). We found that insulin decreased the frequency,
amplitude, and duration of SLEs as well as the synchronic activity of
PFC neurons evoked by 4-AP. These insulin effects were mediated by the
PI3K/Akt signaling pathway and mimicked by gaboxadol (THIP), a delta
GABA(A) receptor agonist. The effect of insulin on the number of SLEs
was partially blocked by L-655,708, an inverse agonist with high
selectivity for GABA(A) receptors containing the alpha 5 subunit. Our
results suggest that insulin reduces neuronal excitability by an
increase of GABAergic tonic currents. The physiological relevance of
these findings is discussed.
Filiaciones:
Villalobos, N.:
Academia de Fisiología, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Ciudad de México, Mexico
Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del IPN, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Ciudad de México, Mexico
Ramirez-Sanchez, E.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Mondragon-Garcia, A.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Garduño J.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Castillo-Rolon, D.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Trujeque-Ramos, S.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Translational Neurogenetics Unit, Wallenberg Neuroscience Center, Lund University, Lund, Sweden
Hernandez-Lopez, S.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
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