Repeated 4-aminopyridine seizures reduce parvalbumin content in the medial mammillary nucleus of the rat brain

Abstract

Parvalbumin (Pv) containing fast spiking neurons play a crucial role in synchronizing the activity of excitatory neuronal circuits in the brain. Alterations of parvalbumin content in these neurons can affect their spike characteristics and, ultimately, may increase the susceptibility of neuronal circuits to epileptic seizures. In the present study, we examined whether repeated 4-aminopyridine (4-AP)-induced seizures modify the regional parvalbumin contents in the rat brain. 4-Aminopyridine was injected intraperitoneally in adult rats, controls received the solvent. Animals were sacrificed at 3 h after a single acute treatment, or following repeated, daily treatments of 12 days. In situ hybridization (ISH) indicated significantly decreased parvalbumin mRNA level in the medial mammillary nucleus (MM) at 12 days. Western blotting revealed 20.1% significant decrease of parvalbumin content in the medial mammillary area, while parvalbumin immunohistochemistry indicated no change of the number of immunoreactive cells in the medial mammillary nucleus. The results reveal the downregulation of the transcription of the parvalbumin gene and the decrease of parvalbumin synthesis in medial mammillary nucleus neurons in response to experimental seizures.