The precise localization of D1 and D2 dopamine receptors within striatal neurons and circuits is crucial information for further understanding dopamine pharmacology. We have used subtype specific polyclonal and monoclonal antibodies against D1 and D2 dopamine receptors to determine their cellular and subcellular distributions, their colocalization, and their differential connectivity with motor cortical afferents labeled either by lesion-induced degeneration or by anterograde transport of biotinylated dextrans. D1 and D2 are primarily expressed in medium-sized neurons and spiny dendrites. Axon terminals containing D1 were rare whereas D2-immunoreactive axon terminals forming symmetrical synapses with dendrites and spines were common. In 2 microns sections, D1 was localized to 53% of neurons, and D2 to 48% of neurons, while mixing D1 and D2 antibodies labeled 78%. By electron microscopy, D1 was localized to 43% of dendrites and 38% of spines while D2 was localized to 38% of dendrites and 48% of spines. Combining D1 and D2 antibodies resulted in the labeling of 88.5% of dendrites and 92.6% of spines. Using different chromogens for D1 and D2, colocalization was not observed. Ipsilateral motor corticostriatal afferents were primarily axospinous and significantly more synapsed with D1 than D2-positive spines (65% vs 47%). Contralateral motor corticostriatal afferents were frequently axodendritic and no difference in their frequency of synapses with D1 and D2 dendrites and spines was observed. These findings demonstrate differential patterns of expression of D1 and D2 receptors in striatal neurons and axon terminals and their differential involvement in motor corticostriatal circuits.
Neurokinin 3 (NK3) receptor is predominantly expressed in striatum and substantia nigra (SN). Evidences have indicated the roles of NK3 receptor in the pathogenesis of Parkinson's disease. By administrating NK3 receptor agonist senktide into 6-hydroxydopamine (6-OHDA)-lesioned rats, exacerbation of dopaminergic degeneration was found in striatum and substantia nigra pars compacta. From apomorphine rotation test, significant increase of contralateral rotation number was detected in 6-OHDA-lesioned rats with senktide injection. Furthermore, tyrosine hydroxylase expression in striatum and substantia nigra pars compacta were examined by immunohistochemistry and Western blotting. Further reduction of tyrosine hydroxylase immunoreactivities was found in 6-OHDA-lesioned rats that received senktide treatment. Also, phosphorylation of N-methyl-D-aspartate receptor 1 subunit was investigated in SN region and significant up-regulation was revealed in senktide-treated 6-OHDA-lesioned rats. Finally, phosphorylation of mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and c-Jun were examined in nigral region. Up-regulation of phosphorylated JNK molecules was shown in SN region after senktide injection. In line with this evidence, phosphorylation of c-Jun at Ser 63 and Ser 73 was also up-regulated by senktide treatment, thus presenting new aspects that NK3 peptide could exacerbate 6-OHDA toxicity in in vivo models and the possible mechanism may be contributed by the modulation of N-methyl-D-aspartate receptor 1 subunit and JNK pathway activities.
The complex and uncertain causes of sick building syndrome (SBS) have become one of the most challenging and hot issues worldwide. Studies on the correlation between indoor environment and SBS based on local characteristics are relatively limited in China. We studied typical SBS risk factors related to the indoor environment and lifestyle in two northern Chinese cities. The study population was drawn from parents of pre-school children in randomized daycare centers in Taiyuan, Shanxi, and Urumqi, Xinjiang, China (N = 6838). Data on SBS and indoor environment were obtained from cross-sectional questionnaires. Odds ratios (OR) were estimated by multilevel logistic regression and adjusted using gender, atopy, own smoking, home size, and dampness index. Results showed that location, homeownership, year of construction completion, changes in the indoor environment (new furniture and decorations), and changes in indoor air (smoking, burning mosquito repellent and incense, cooking fuels including electricity, natural gas, coal, and wood) might contribute to different levels of SBS in Chinese adults, including eye, nasal, throat, dermal symptoms, and headache and tiredness. The results of the subgroup analysis suggest city and gender differences in susceptibility. Daily cleaning, window opening, and improved ventilation effectively improved SBS. People should improve their indoor environment and lifestyles based on sensitivity factors, gender, and geographic characteristics to reduce SBS risks.
Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative disorders, with an overall global incidence of 40 million. Many studies have revealed the association of intestinal disorders and bacterial infections with PD, but few studies have found such a relationship with AD. In this meta-analysis, related articles published up to September 2018 were searched in PubMed. Of the 2121 related articles screened initially, 56 were found to be eligible. Data on the risks of PD and AD due to five intestinal disorders and infection with Helicobacter pylori, as a representative intestinal microbe, were obtained, and a fixed- or random-effects model was used to pool the odds ratios (ORs) with 95% confidence interval (CIs) from individual studies. The combined OR for all types of intestinal disorders with an increased risk of PD was 3.36 (95% CI: 2.70–4.17). The ORs for each category were as follows: constipation, 4.05 (95% CI, 3.24–5.06); inflammatory bowel disease (IBD), 1.16 (95% CI, 0.89–1.52); irritable bowel syndrome (IBS), 1.75 (95% CI, 0.55–5.56); small intestinal bacterial overgrowth, 5.15 (95% CI, 3.33–7.96); and diarrhea, 1.27 (95% CI, 0.28–5.75). The combined OR of all types of intestinal disorders with an increased risk of AD was 1.52 (95% CI, 1.09–2.13). The ORs for IBS and IBD were 1.42 (95% CI, 1.02–1.99) and 2.40 (95% CI, 1.00–5.76), respectively. The risk estimates of H. pylori infection in PD and AD patients were as follows: OR, 1.65 (95% CI, 1.43–1.91) and OR, 1.40 (95% CI, 1.12–1.76), respectively. These findings suggest that PD and AD are significantly associated with intestinal disorders. The negative roles of H. pylori in the development of PD or AD should be evaluated to shed new light on the diagnosis and treatment of PD and AD. National governments should periodically inspect the intestinal condition of residents and extend health plans to improve intestinal health to prevent potential neurological disorders.
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