The D2 dopamine receptor (Drd2) is implicated in several brain disorders such as schizophrenia, Parkinson’s disease, and drug addiction. Drd2 is also the primary target of both antipsychotics and Parkinson’s disease medications. Although the expression pattern of Drd2 is relatively well known in mouse brain, the temporal and spatial distribution of Drd2 is lesser clear in rat brain due to the lack of Drd2 reporter rat lines. Here, we used CRISPR/Cas9 techniques to generate two knockin rat lines: Drd2::Cre and Rosa26::loxp-stop-loxp-tdTomato. By crossing these two lines, we produced Drd2 reporter rats expressing the fluorescence protein tdTomato under the control of the endogenous Drd2 promoter. Using fluorescence imaging and unbiased stereology, we revealed the cellular expression pattern of Drd2 in adult and postnatal rat forebrain. Strikingly, the Drd2 expression pattern differs between Drd2 reporter rats and Drd2 reporter mice generated by BAC transgene in prefrontal cortex and hippocampus. These results provide fundamental information needed for the study of Drd2 function in rat forebrain. The Drd2::Cre rats generated here may represent a useful tool to study the function of neuronal populations expressing Drd2.
Cortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Nav1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Nav currents. Intriguingly, activation of GABAergic interneurons or restoring NRG1 expression in adulthood could rescue the hyperactivity and impaired social novelty in gtoNrg1 mice. These results identify mechanisms underlying cortical disinhibition related to schizophrenia and raise the possibility that restoration of NRG1 signaling and GABAergic function is beneficial in certain neuropsychiatric disorders.
Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P < 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.
Objective:The purpose of this study was to validate a Chinese version of the modified Standardized Swallowing Assessment (SSA) instrument used by nurses in stroke patients with dysphagia and explore the feasibility of the simplified instrument.Materials and Methods:This study involved a cross-sectional design. Nurses independently applied the modified SSA to 127 patients with stroke before a complete dysphagia evaluation conducted by a speech–language pathologist. Factor analysis of eight dysphagia variables in the modified SSA was performed to evaluate construct validity. The accuracy of the screening instrument was assessed through receiver operating characteristic (ROC) analysis.Results:The comprehensive swallowing assessment revealed that 49.6% of the stroke patients had dysphagia. The modified SSA had an acceptable internal consistency coefficient. The inter-rater agreement between nurses using the modified SSA showed a Kappa coefficient of 0.509. All items had a communality loading of >0.5, and two factors accounted for 73.89% of the response variance. The area under the ROC curve was 0.79 (95% confidence interval: 0.71–0.87). The sensitivity and specificity derived for dysphagia detection were satisfactory according to the results obtained from the original 8-item and simplified 6-item scales (sensitivities = 82.50% and 81.00% and specificities = 59.40% and 64.10%, respectively; accuracy = 70.87% and 72.44%, respectively).Conclusion:This preliminary study suggests that the modified SSA is a potentially reliable and valid nurse-administered screening instrument for dysphagia detection in patients with stroke.
Neuregulin 1 (Nrg1) encodes a neurotrophic factor and is genetically associated with schizophrenia, bipolar disorder and major depression. NRG1 has been shown to play important roles in neurodevelopment and neurotransmission. However, the knowledge about the cellular expression pattern of Nrg1 in mouse forebrain remains controversial and inconclusive. Here we used CRISPR/Cas9 techniques to generate Nrg1Cre/+ knockin mice which express the Cre recombinase immediately before the stop codon of Nrg1 gene. By crossing the Nrg1Cre/+ mice with Ai14 reporter mice which express fluorescent protein tdTomato in a Cre-dependent manner, we generated Nrg1 reporter mice which express tdTomato in cells where Nrg1 gene is actively transcribed. Using fluorescence imaging and unbiased stereology, we revealed the cellular expression pattern of Nrg1 in mouse forebrain regions including the olfactory bulb, cerebral cortex, striatum and hippocampus. We further performed stereotaxic injection of adeno-associated virus (AAV) which express tdTomato in a Cre-dependent way into different forebrain regions of adult Nrg1Cre/+ mice, and thus explored the distribution and axon projection of Nrg1-positive cells. These results provide fundamental information needed for the study of Nrg1 function in mouse forebrain. Moreover, the Nrg1Cre/+ mice generated here may represent a useful tool to study the function of neuronal populations expressing Nrg1.
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