Objective To investigate the effect and mechanism of interfering the nicotinamide mononucleotide adenylyltransferase 1(NMNAT1)gene in Parkinson's disease(PD)mouse models. Methods Thirty mice were randomly assigned to three groups: the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group, the small interfering nicotinamide mononucleotide adenylyltransferase 1 (siNMNAT1)+MPTP group, and the control group, with 10 mice in each group.After injecting siRNA-green fluorescent protein(GFP)lentivirals directly into substantia nigra(SN),mice received intraperitoneal injections of MPTP, which was the siNMNAT1 +MPTP group.While the MPTP group was only with injections of MPTP,and the control group was with neither siRNA nor MPTP.Then we assessed the motor coordination ability firstly.To observe the variation of nigrostriatal pathway, the counts of dopamanergic neurons in SN were measured by tyrosine hydroxylase(TH)immunofluorescence staining.And the expression of TH in striatum, which was used to estimate the dopaminergic neurons axonal variation, was analyzed by RT-PCR.Then the expression of TH, SOD1, Bcl2, Bax, Bcl2/Bax in SN was estimated through Western blotting.Results Compared with the control group,the siNMNAT1+MPTP group and the MPTP group decreased significantly in motor coordination ability(creep down time: siNMNAT1 +MPTP group(62.8 ±15.7)s,MPTP group(77.9 ±13.5)s, control group(122.0 ±25.2)s), dopamanergic neuron counts(siNMNAT1 +MPTP group 45.0 ±6.7, MPTP group 68.0 ±11.3, control group 93.0 ± 12.8)and the striatal TH expression(Creep down time: t=-6.291, P=0.000; t=-4.865, P=0.000.Dopamanergic neuron counts:t=-10.482,P=0.000;t=-4.624, P=0.000.TH expression:t=-9.117,P=0.000;t=-5.716, P=0.000).Although the siNMNAT1+MPTP group showed lower coordination ability than the MPTP group, there was no statistically significant difference.Whereas the counts of dopamanergic neurons in SN(t=-5.487, P=0.000), the expression of TH in striatum(t=-5.146,P=0.003),SOD1(t=-4.143, P=0.001)and Bcl2/Bax(t=-6.303, P=0.000)were obviously decreased in the siNMNAT1+MPTP group,in which Bax increased significantly(t=3.550,P=0.002).Conclusions Interfering the expression of NMNAT1 aggravated the neurodegeneration in PD, and the mechanism might be related to oxidative stress and programmed cell death.

OBJECTIVE: To estimate the social and economic burden of Downs syndrome for patients and their families residing in Changsha, China. METHODS: An 160-item self-administered questionnaire was designed and distributed to the primary caregivers of the patients in March 2020. A total of 81 eligible participants had completed the questionnaire, among which 20 were excluded for incomplete data. A patient perspective was taken to estimate the economic burden of the disease. The social impact of the disease on the patient's family was evaluated through questions adapted from the Stanford Psychological Wellbeing (PWB) Scale. RESULTS: The estimated life-course cost of a Downs syndrome patient in Changsha is 4 985 659 RMB, with the patient and caregiver's loss of income taking the greater proportion. In addition, as the majority of the patients' primary caregivers, female caregivers experienced not only considerable financial hardship caused by the care provision, but also a significant amount of psychological pressure and social discrimination. CONCLUSION Increased level of social welfare for the patients and social support for their female caregivers are essential for reducing economic burden and improving their quality of life in the area. In addition, prenatal screening and diagnosis for Downs syndrome are important for reducing both the social and economic burden of the disease by preventing its occurrence.
Caregivers ; China ; Down Syndrome ; Female ; Financial Stress ; Humans ; Quality of Life ; Social Discrimination ; Surveys and Questionnaires

ObjectiveTo investigate the therapeutic effect of Qinggongtang in regulating Glu/GABA metabolic balance and the mechanism of its anxiolytic effect on rat models of anxiety. MethodFifty-four rats were randomly divided into normal， model， diazepam （0.225 mg·kg^-1）， and low-dose， medium-dose， and high-dose groups of Qinggongtang （5.085， 10.17， 20.34 g·kg^-1）， with nine rats in each group. Except for the normal group， the other groups were subjected to indeterminate vacutainer stress and chronic restraint stress for 12 days to prepare the anxiety model. On the 3^rd day of the stress， 10 days of corresponding drug intervention was started. At the end of the drug treatment， the anxiety level of rats in each group was evaluated by the elevated cross maze experiment （EPM） and the light and dark box experiment （LDB）， and the effect of Qinggongtang on the anxiety behavior of rats was preliminarily analyzed. The levels of Glu and GABA in the amygdala tissue of the rats were detected by enzyme linked immunosorbent assay （ELISA）， and the changes in the synaptic ultrastructure of the amygdala of the rats in each group were observed by electron microscopy. The mRNA expression of glutamic acid decarboxylase （GAD65 and GAD67）， glutamine synthetase （GS）， and glutamate transporter-1 （GLT-1） in the amygdala were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and their protein expression was detected by Western blot. ResultCompared with those in the normal group， rats in the model group showed an obvious anxiety state and dull yellow and lusterless fur. They were irritable， easy to anger， and preferred to curl up in the corner. The number of times the EPM entered the open arm and the residence time in the open arm were significantly reduced （P<0.01）， and the residence time in the open box and the number of times the LDB went through the box were significantly reduced （P<0.01）. The content of Glu in the amygdala was increased （P<0.01）， and the content of GABA was reduced （P<0.01）. The value of Glu/GAB was elevated （P<0.01）， and the number of synaptic and pre-synaptic membrane vesicles in the amygdala was decreased. Sparse dense material in the post-synaptic membrane， increased synaptic gap， slightly disrupted internal structure， and decreased mRNA and protein expressions of GAD65， GAD67， GS， and GLT-1 in the amygdala were observed （P<0.01）. Compared with those in the model group， rats in the medium-dose and high-dose groups of Qinggongtang and the diazepam group had bright fur， sensitive reactions， and more active behavior. The number of times EPM entered the open arm and the residence time in the open arm increased significantly （P<0.01）， and the residence time in the open box and the number of times the LDB went through the box increased significantly （P<0.01）. The content of Glu in all-dose groups of Qinggongtang and the diazepam group decreased （P<0.05， P<0.01）， while GABA content increased （P<0.05， P<0.01）. The value of Glu/GABA decreased （P<0.01）， and the internal and external synaptic structure of each groups of Qinggongtang and the diazepam group was more complete. Synapses and vesicles were numerous， and the synaptic gap was more clearly defined. The efficacy of the high-dose group of Qinggongtang and the diazepam group was the best， and the mRNA and protein expressions of GAD65， GAD67， GS， and GLT-1 in the amygdala were increased in the high-dose group of Qinggongtang and diazepam group （P<0.05， P<0.01）. ConclusionQinggongtang can improve synaptic plasticity and affect the expression of GAD65， GAD67， GS， and GLT-1 in the amygdala of rats to regulate Glu/GABA metabolic balance and thus exert anxiolytic effects.