Impact of chronic lithium treatment on brain oxidative stress and anxiety-like behaviors in rats: Dose-dependent effects.

Lithium (Li) is a mood-stabilizing drug. Although one of the potential mechanisms underlying the neuroprotective effects of lithium is related to its antioxidative effect, its mechanisms of action are not fully understood. Herein we aimed to investigate the impact of varied dosages of long-term lithium therapy on oxidative stress parameters in the brains of healthy rats, and on anxiety-like behaviors, and whether any changes in behavior can be attributed to modifications in oxidative stress levels within the brain. Thirty-two adult Wistar albino male rats were randomly assigned to four treatment groups. While the control (C) group was fed with a standard diet, low Li (1.4 g/kg/diet), moderate Li (1.8 g/kg/diet), and high Li (2.2 g/kg/diet) groups were fed with lithium bicarbonate (Li2CO3) for 30 days. Malondialdehyde increased, while superoxide dismutase and catalase levels decreased in the brains of the high Li group animals. In addition, anxiety-like behaviors of animals increased in the high Li group considering fewer entries to and less time spent in the open arms of the elevated plus maze test. Our findings underscore the potential adverse effects of prolonged lithium treatment, especially at doses approaching the upper therapeutic range. The induction of toxicity, manifested through heightened oxidative stress, appears to be a key mechanism contributing to the observed increase in anxiety-like behaviors. Consequently, caution is warranted when considering extended lithium therapy at higher doses, emphasizing the need for further research to delineate the precise mechanisms underlying these effects and to inform safer therapeutic practices.

PRNP gene polymorphisms in main indigenous Turkish goat breeds.

The polymorphisms of the PRNP gene influence the susceptibility to scrapie in goats. In this study, caprine PRNP gene was analysed in a total of 249 individuals from three main indigenous goat breeds of Turkey: Anatolian Black, Angora and Kilis. We focused on the Anatolian Black breed, which represents 97% of the goat population in Turkey and compared the data of samples originated from different geographical regions. Eight polymorphisms were determined, given rise to 12 haplotypes. Allele, genotype and haplotype frequencies of the polymorphisms at codons 142, 143, 146, 154, 171, 211, 222 and 240 were calculated. Alleles associated to resistance to scrapie were found to be relatively rare in all breeds. The resistance allele 222K was absent in Turkish breeds. Other resistance-associated alleles: 146D, 146S, 154H and 171R were observed with low frequencies. The results of this study, which cover the mainly bred indigenous goats in Turkey, present the distribution of PRNP polymorphisms. Very low frequencies of resistance-associated alleles show the susceptibility to scrapie. The resistance-associated alleles S and D of codon 146 might be accepted as candidate alleles, due to their relative higher frequencies observed in the present study. A breeding program aiming to increase particularly the frequency of 146S might be applied. Predictions about impacts of a long-term breeding programme based on low initial allele frequencies and regarding its possible adverse effects are warranted. Our results might be a database for future breeding programmes, which should be carefully designed with adequate levels of genetic resistance and acceptable timeframe.