RESUMO
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.
RESUMO
Sulfamonomethoxine (SMM) is widely used in the veterinary field in China. Although some clinical surveys have revealed that sulfonamide antibiotics cause adverse nervous system symptoms, the related mechanisms of maternal SMM exposure on the neurobehavioral development of offspring remain unclear. Here, we investigated the effects of perinatal SMM exposure on the physiological and behavioral responses of pubertal offspring mice and the underlying mechanisms. We randomly allocated pregnant mice into the groups treated with SMM at different doses and the saline-treated groups. Maternal mice were orally administered SMM daily from gestational day 1 to postpartum day 21. On postnatal day (PND) 22, the parameters of growth, endocrine hormones, and brain amino acid composition were assessed, as well as the brain transcript levels of key genes involved in the mammalian target of rapamycin (mTOR) signaling pathway. From PND 50 to 55, a battery of behavioral tests relevant to anxiety and memory were then administered. Analysis of the results indicated that the pups, particularly the pubertal female offspring, showed anxiety-like behavior. Moreover, the pubertal offspring showed cognitive impairments and fat accumulation. Furthermore, the relative mRNA expression of genes involved in the mTOR signaling pathway in females on PND 22 was elevated, whereas the expression of N-methyl-d-aspartate receptor 2B (NR2B) was reduced. Together, the results showed that perinatal SMM exposure perturbs neuroendocrine functions, and further alters gene expression in the mTOR pathway and NR2B gene expression early in life, which may contribute to brain dysfunction in pubertal life.