The tryptophan (Trp) metabolite kynurenic acid (KYNA) is an α7-nicotinic and N-methyl-d-aspartate receptor antagonist. Elevated brain KYNA levels are commonly seen in psychiatric disorders and neurodegenerative diseases and may be related to cognitive impairments. Recently, we showed that N-acetylcysteine (NAC) inhibits kynurenine aminotransferase II (KAT II), KYNA’s key biosynthetic enzyme, and reduces KYNA neosynthesis in rats in vivo. In this study, we examined if repeated systemic administration of NAC influences brain KYNA and cognitive performance in mice. Animals received NAC (100 mg/kg, i.p.) daily for 7 days. Redox markers, KYNA levels, and KAT II activity were determined in the brain. We also assessed the effect of repeated NAC treatment on Trp catabolism using brain tissue slices ex vivo. Finally, learning and memory was evaluated with and without an acute challenge with KYNA’s bioprecursor L-kynurenine (Kyn; 100 mg/kg). Subchronic NAC administration protected against an acute pro-oxidant challenge, decreased KYNA levels, and lowered KAT II activity and improved memory both under basal conditions and after acute Kyn treatment. In tissue slices from these mice, KYNA neosynthesis from Trp or Kyn was reduced. Together, our data indicate that prolonged treatment with NAC may enhance memory at least in part by reducing brain KYNA levels.

Glioblastoma is the most aggressive brain tumor with a low median survival of 14 months. The only Food and Drug Administration (FDA)-approved treatment for topical delivery of the cancer drug carmustine is Gliadel. However, its use has been associated with several side-effects, mainly provoked by a mass effect. Nitrogen-doped carbon nanotube sponges (N-CNSs) are a new type of nanomaterial exhibiting high biocompatibility, and they are able to load large amounts of hydrophobic drugs, reducing the amount of carriers. This study evaluated the use of N-CNSs as potential carmustine carriers using malignant glioma cell lines. N-CNSs were characterized by nanoparticle tracking analysis and transmission electron microscopy. The biocompatibility of N-CNSs was determined in glioma cell lines and in primary astrocytes. Afterward, N-CNSs were loaded with carmustine (1:10 w/w), and the drug and liberation efficiency, as well as cytotoxicity induction, were determined. N-CNSs presented a homogeneous size distribution formed by round nanotubes, without induced cytotoxicity, at concentrations below 40 µg/mL. The N-CNSs loaded with carmustine exhibited a continuous kinetic release of carmustine with a maximum release after 72 h. The cytotoxic effect of N-CNSs loaded with carmustine was similar to that of carmustine alone. The results demonstrated that N-CNSs are a biocompatible nanostructure that could be used as carriers for the tumoral load of large amounts of chemotherapeutic agents.

The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. Toxoplasma gondii is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels of IgG anti-T. gondii from mothers and their neonates, with a higher risk of developing schizophrenia. The absence of the parasite and the levels of IgGs found in the early stages of life suggest a transplacental transfer of the anti-T. gondii IgG antibodies, which could bind fetal brain structures by molecular mimicry and induce alterations in neurodevelopment. This study aimed to determine the maternal pathogenic antibodies formation that led to behavioral impairment on the progeny of rats immunized with T. gondii. Female rats were immunized prior to gestation with T. gondii lysate (3 times/once per week). The anti-T. gondii IgG levels were determined in the serum of pregestational exposed females’ previous mating. After this, locomotor activity, cognitive and social tests were performed. Cortical neurotransmitter levels for dopamine and glutamate were evaluated at 60 PND in the progeny of rats immunized before gestation (Pregestational group). The maternal pathogenic antibodies were evidenced by their binding to fetal brain mimotopes in the Pregestational group and the reactivity of the serum containing anti-T. gondii IgG was tested in control fetal brains (non-immunized). These results showed that the Pregestational group presented impairment in short and long-term memory, hypoactivity and alteration in social behavior, which was also associated with a decrease in cortical glutamate and dopamine levels. We also found the IgG antibodies bound to brain mimotopes in fetuses from females immunized with T. gondii, as well as observing a strong reactivity of the serum females immunized for fetal brain structures of fetuses from unimmunized mothers. Our results suggest that the exposure to T. gondii before gestation produced maternal pathogenic antibodies that can recognize fetal brain mimotopes and lead to neurochemical and behavioral alterations in the offspring.