ABSTRACT
Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.
ABSTRACT
Background and purpose:The non-small cell lung cancer (NSCLC) has been the highest disease incidence in lung cancer, sputum cytology diagnosis has become an important adjunct to the early diagnosis of lung cancer. The purpose of this study was to investigate the value of thinprep cytological and immunocytochemical method in differentiatial diagnosis of exfoliated cells of malignant sputum in NSCLC. Methods:Sputum samples were detected with thinprep cytology test, a total of 530 cases suspicious tumor cells and malignant tumor cells sputum specimens were randomly selected in continuous paraffin-embedded sections, respectively, NSCLC tumor cell markers CK7, CK5/6, TTF-1, P63, EMA were evaluted by immunocytochemical staining. Results:Of the 530 cases of malignant sputum, these were confirmed 265 cases of lung adenocarcinoma, 246 cases of squamous carcinoma, 19 cases of adeno-squamous carcinoma. Moreover, TTF-1 and CK7 were signiifcantly higher expressed in adenocarcinoma, the positive rates were 92.45%(245/265) and 91.70%(243/265);CK5/6 and P63 were signiifcantly higher expressed in squamous carcinoma, the positive rates were 97.15% (239/246) and 99.59% (245/246). Conclusion: Liquid-based cytology combined with immunocytochemistry had important clinical value in classification and identification of sputum samples, the combination of CK7, CK5/6, TTF-1, P63, EMA can be used for classiifcation and identiifcation of malignant sputum samples between NSCLC, is worthy of promoting in clinical cytopathology diagnosis.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the neuroprotective effects and mechanisms of Chunxiong Chatiao pulvis (CXCT) on the MPTP-induced dopaminergic neurodegneration in mice model of PD.</p><p><b>METHOD</b>Three to five months old male mice were randomly divided into following six treatment groups (NS + NS, 50 mg x kg(-1) CXCT + NS, 25 mg x kg(-1) CXCT + MPTP, 50 mg x kg(-1) CXCT + MPTP, 75 mg x kg(-1) CXCT + MPTP, NS + MPTP) (n = 8/group). For behavioral measurement, the mice were evaluated for their motor coordination by pole-test; Striatal dopamine content of mice was measured using standard reverse-phase HPLC; Number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra of mice was detected by immunohistochemistry; SOD activity in the substantia nigra of mice were measured by fluorimetry.</p><p><b>RESULT</b>The score of pole test (25, 50, 75 mg x kg(-1)), the striatal dopamine contents (75 mg x kg-1), the residual DA contents (75 mg x kg(-1)) and the SOD activity in substantia nigra (50, 75 mg x kg(-1)) all showed that, the CXCT-pretreated groups significantly higher than that of the group NS + MPTP (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Chuanxiong Chatiao pulvis improved the motor deficit in MPTP-induced mice, and attenuate MPTP-induced dopaminergic neurodegeneration in mice. Importantly, the neuroprotective effect of Chuanxiong Chatiao pulvis against dopaminergic neurodegeneration may be associated with its strong antioxidant capacity in vivo.</p>