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Purpose and background: Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods: Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results: CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion: Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI. [ABSTRACT FROM AUTHOR]

Although emerging evidence has revealed that LHPP, a histidine phosphatase protein, suppresses the progression of different cancers, a pan-cancer analysis still remains unavailable. Therefore, we first utilized different bioinformatics tools to explore the tumor inhibitory role of LHPP protein across 33 tumor types based on the TCGA project. Additionally, HGC-27 gastric cancer cells were used to evaluate the biological functions of LHPP after stable transfection with lentiviruses. Consequently, LHPP mRNA and protein expression were down-regulated in the most cancer tissues corresponding to normal tissues. The data showed that patients with higher LHPP performance had a better prognosis of overall survival (OS) and disease-free survival (DFS) in brain glioma and renal carcinoma. In addition, we found that enhancement of LHPP expression attenuated the proliferation, migration and invasion of gastric cancer cells. The expression levels of cell-cycle-related and EMT-related molecules, such as CDK4, CyclinD1, Vimentin and Snail, were clearly reduced. Moreover, a genetic alteration analysis showed that the most frequent mutation types in LHPP protein was amplification. The patients without LHPP mutation showed a better tendency of prognosis in UCEC, STAD and COAD. Cancer-associated fibroblast infiltration was also observed in head and neck squamous cell carcinoma, stomach adenocarcinoma and testicular germ cell tumors. In summary, our pancancer analysis among various tumor types could provide a comprehensive understanding of LHPP biological function in the progression of malignant diseases and promote the development of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Due to heterogeneous clinical presentation, difficult differential diagnosis with Alzheimer's disease (AD) and psychiatric disorders, and evolving clinical criteria, the epidemiology and natural history of frontotemporal lobar degeneration (FTD) remain elusive. In order to better characterize FTD patients, we relied on the database of a regional memory clinic network with standardized diagnostic procedures and chose AD patients as a comparator. Methods: Patients that were first referred to our network between January 2010 and December 2016 and whose last clinical diagnosis was degenerative or vascular dementia were included. Comparisons were conducted between FTD and AD as well as between the different FTD syndromes, divided into language variants (lvFTD), behavioral variant (bvFTD), and FTD with primarily motor symptoms (mFTD). Cognitive progression was estimated with the yearly decline in Mini Mental State Examination (MMSE). Results: Among the patients that were referred to our network in the 6-year time span, 690 were ultimately diagnosed with FTD and 18,831 with AD. Patients with FTD syndromes represented 2.6% of all-cause dementias. The age-standardized incidence was 2.90 per 100,000 person-year and incidence peaked between 75 and 79 years. Compared to AD, patients with FTD syndromes had a longer referral delay and delay to diagnosis. Patients with FTD syndromes had a higher MMSE score than AD at first referral while their progression was similar. mFTD patients had the shortest survival while survival in bvFTD, lvFTD, and AD did not significantly differ. FTD patients, especially those with the behavioral variant, received more antidepressants, anxiolytics, and antipsychotics than AD patients. Conclusions: FTD syndromes differ with AD in characteristics at baseline, progression rate, and treatment. Despite a broad use of the new diagnostic criteria in an organized memory clinic network, FTD syndromes are longer to diagnose and account for a low proportion of dementia cases, suggesting persistent underdiagnosis. Congruent with recent publications, the late peak of incidence warns against considering FTD as being exclusively a young-onset dementia. [ABSTRACT FROM AUTHOR]