Abstract
This study aimed to evaluate the possible protective role of taurine on anxiety-like behavior, brain electrical activity and glial cell immunoreactivity in well-nourished and malnourished rats that were treated with a subconvulsing dose of pilocarpine. Newborn Wistar rats were subjected to normal or unfavorable lactation conditions, represented by the suckling of litters with 9 or 15 pups, resulting in well-nourished and malnourished animals, respectively. Each nutritional group was split into five subgroups that were treated from postnatal day (PND) 35 to 55 with 300 mg/kg/day of taurine + 45 mg/kg/day of pilocarpine (group T + P), taurine only (group T), pilocarpine only (group P), vehicle control (group V), or not treated control (group naïve; Nv). At PND56-58, the groups were subjected to the elevated plus-maze behavioral tests. Glycemia was measured on PND59. Between PND60 and PND65, the cortical spreading depression (CSD) was recorded in the cerebral cortex, and the levels of malondialdehyde and microglial and astrocyte immunoreactivity were evaluated in the cortex and hippocampus. Our data indicate that treatment with taurine and pilocarpine resulted in anxiolytic-like and anxiogenic behavior, respectively, and that nutritional deficiency modulated these effects. Both treatments decelerated CSD propagation and modulated GFAP- and Iba1-containing glial cells. Pilocarpine reduced body weight and glycemia, and administration of taurine was not able to attenuate the effects of pilocarpine. The molecular mechanisms underlying taurine action on behavioral and electrophysiological parameters in the normal and altered brain remain to be further explored.
Highlights
Taurine is an amino sulfonic acid that is found abundantly in several areas of the mammalian central nervous system
This acute phase is followed by a condition of permanent recurrent spontaneous seizures, altering the central nervous system structure and function (Turski et al, 1989) with behavioral and electroencephalographic changes that are similar to those observed in human temporal lobe epilepsy
Weaning occurred on postnatal day (PND) 21, when pups were separated by sex and housed in polypropylene cages (51 cm × 35.5 cm × 18.5 cm; three rats per cage) under a 12-h light:12-h dark cycle, controlled temperature (23 ± 1◦C), and with free access to water and the same commercial lab chow, with 23% protein, that was offered to their dams during the lactation period (Purina, Ltd.)
Summary
Taurine is an amino sulfonic acid that is found abundantly in several areas of the mammalian central nervous system. The acute systemic injection of pilocarpine in rodents constitutes an effective, experimental model largely used to study the pathophysiology of seizures and to identify potential therapeutic agents for the treatment of epilepsy (Santos et al, 2000) This model was first described by Turski et al (1983a,b)); it consists of the single administration of a high dose (300– 380 mg/kg; Guedes and Cavalheiro, 1997) or various consecutive low doses of pilocarpine until induction of status epilepticus (Glien et al, 2001). Under subconvulsing paradigms several reports have described anxietylike behavioral profiles (Duarte et al, 2014; Francisco and Guedes, 2018), reductions in glycemia (Francisco and Guedes, 2018), increases in brain oxidative stress (Mendes-da-Silva et al, 2018) and impairment of propagation of the excitability-related phenomenon known as cortical spreading depression (CSD) along the cortical rodent tissue (Francisco and Guedes, 2018; Mendes-da-Silva et al, 2018)
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