Huntington’s disease (HD) is a heritable neurological disorder that affects cognitive and motor performance in patients carrying the mutated huntingtin (HTT) gene. In mouse models of HD, previous reports showed a significant increase in spontaneous GABA A receptor-mediated synaptic activity in striatal spiny projection neurons (SPNs). In this study, using optogenetics and slice electrophysiology, we examined the contribution of γ-aminobutyric acid (GABA)-ergic parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons to the increase in GABA neurotransmission using the Q175 (heterozygote) mouse model of HD. Patch clamp recordings in voltage-clamp mode were performed on SPNs from brain slices of presymptomatic (2 months) and symptomatic (8 and 12 months) Q175 mice and wildtype (WT) littermates. While inhibitory postsynaptic currents (IPSCs) evoked in SPNs following optical activation of PV- and SOM-expressing interneurons differed in amplitude, no genotype-dependent differences were observed at all ages from both interneuron types; however, responses evoked by either type were found to have faster kinetics in symptomatic mice. Since SOM-expressing interneurons are constitutively active in striatal brain slices, we then examined the effects of acutely silencing these neurons in symptomatic mice with enhanced Natronomonas pharaonis halorhodopsin (eNpHR). Optically silencing SOM-expressing interneurons resulted in a greater decrease in the frequency of spontaneous IPSCs (sIPSCs) in a subset of SPNs from Q175 mice compared to WTs, suggesting that SOM-expressing interneurons are the main contributors to the overall increased GABA synaptic activity in HD SPNs. Additionally, the effects of activating GABA B and cannabinoid (CB1) receptors were investigated to determine whether these receptors were involved in modulating interneuron-specific GABA synaptic transmission and if this modulation differed in HD mice. When selectively activating PV- and SOM-expressing interneurons in the presence of the CB1 receptor agonist WIN-55,212, the magnitudes of the evoked IPSCs in SPNs decreased for both interneuron types although this change was less prominent in symptomatic Q175 SPNs during SOM-expressing interneuron activation. Overall, these findings show that dysfunction of SOM-expressing interneurons contributes to the increased GABA synaptic activity found in HD mouse models and that dysregulation of the endocannabinoid system may contribute to this effect.
All women belonging to these two communes who had a pregnancy that terminated in 1980 were included in the study. A total of 962 such pregnancies were identified, and 917 of these women (95.3 per cent) were interviewed; 45 were lost to follow-up, having moved elsewhere. ProcedureInitially, the study group developed a questionnaire and gave training sessions to the barefoot doctors in the two study communes and to workers in the County MCH Station who were to participate in the investigation. The training included how to take a good pregnancy history and how to fill out the special questionnaire. The barefoot doctors were then asked to make a list of the names of all women whose pregnancy had terminated in 1980 and the outcomes of these pregnancies, including spontaneous abortions, stillbirths, twins, congenital anomalies, and neonatal deaths. This was a fairly straightforward process since the barefoot doctors in each brigade kept very good records on all pregnant women in their area. Women who had had induced abortions were excluded from this study. The obstetric histories for each of the women in the study were copied from records in the hospitals where they had their deliveries. These hospitals are the commune hospitals, the two county hospitals, and hospitals in the city of Shanghai itself, especially the International Peace Hospital for Women. The workers (primarily physicians) at the County MCH Station abstracted the data from the records, and then the barefoot doctors filled in the remaining part of each questionnaire through home visits and interviews. Finally, all the data were tabulated and analyzed by members of the Maternal and Child Health Research Cooperative Group. Table 1 summarizes the 1980 pregnancies investigated in the two communes. Of 917 pregnancies that could be followed up, 898 (97.9 per cent) terminated as live births (891 single births and seven women with twins), nine (1.0 per cent) involved an intrapartum fetal death or stillbirth (one of the latter was a twin whose mother is also counted under live *Group leader Prof. Xu Sy-en. births for the other twin), and 11 (1.2 per cent) were spontaneous abortions. Seven babies died during the neonatal period, and there was one maternal death. ResultsAmong the 917 women studied, 448 were farm workers (48.9 per cent), 359 were commune factory workers (39.1 per cent), and 110 were city factory workers (12.0 per cent).Fifty per cent of the mothers had a middle school education, 45 per cent had a primary school education, 5 per cent had no formal education, and only one had been to college.With the current emphasis on one-child families and late marriage, it was of considerable interest to examine the parity and age at marriage of the women. At the time of the study, 71 per cent were para 1 and 27 per cent were para 2. Only 15 mothers were para 3 or 4. The majority of the women (64 per cent) had been married at 25-29 years of age, and 34 per cent had been married at 20-24 years of age. Three women had been under 20 at the time of their marriage, wh...
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