Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys.

BACKGROUND: The significantly increasing incidence of type 2 diabetes mellitus (T2DM) over the last few decades triggers the demands of T2DM animal models to explore the pathogenesis, prevention, and therapy of the disease. The altered lipid metabolism may play an important role in the pathogenesis and progression of T2DM. However, the characterization of molecular lipid species in fasting serum related to T2DM cynomolgus monkeys is still underrecognized. METHODS: Untargeted and targeted LC-mass spectrometry (MS)/MS-based lipidomics approaches were applied to characterize and compare the fasting serum lipidomic profiles of T2DM cynomolgus monkeys and the healthy controls. RESULTS: Multivariate analysis revealed that 196 and 64 lipid molecules differentially expressed in serum samples using untargeted and targeted lipidomics as the comparison between the disease group and healthy group, respectively. Furthermore, the comparative analysis of differential serum lipid metabolites obtained by untargeted and targeted lipidomics approaches, four common serum lipid species (phosphatidylcholine [18:0_22:4], lysophosphatidylcholine [14:0], phosphatidylethanolamine [PE] [16:1_18:2], and PE [18:0_22:4]) were identified as potential biomarkers and all of which were found to be downregulated. By analyzing the metabolic pathway, glycerophospholipid metabolism was associated with the pathogenesis of T2DM cynomolgus monkeys. CONCLUSION: The study found that four downregulated serum lipid species could serve as novel potential biomarkers of T2DM cynomolgus monkeys. Glycerophospholipid metabolism was filtered out as the potential therapeutic target pathway of T2DM progression. Our results showed that the identified biomarkers may offer a novel tool for tracking disease progression and response to therapeutic interventions.

China is facing serious experimental monkey shortage during the COVID-19 lockdown.

This report aims to analyze the experimental monkey shortage generated by the COVID-19 lockdown. The supply capability of the monkey breeding farms is insufficient to meet demand, and the sales prices have skyrocketed since 2018. The contradiction will be further aggravated with import prohibition although the countermeasures suggested.

The Faster-Onset Antidepressant Effects of Hypidone Hydrochloride (YL-0919) in Monkeys Subjected to Chronic Unpredictable Stress.

Given the limited monkey models of depression available to date, as well as the procedural complexity and time investments that they involve, the ability to test the efficacy and time course of antidepressants in monkey models is greatly restricted. The present study attempted to build a simple and feasible monkey model of depression with chronic unpredictable stress (CUS) and evaluate the antidepressant effect and onset time of fluoxetine hydrochloride (FLX) and the new drug hypidone hydrochloride (YL-0919), a potent and selective 5-HT reuptake inhibitor, 5-HT1A receptor partial agonist and 5-HT6 receptor full agonist. Female cynomolgus monkeys with low social status in their colonies were selected and subjected to CUS for 8 weeks by means of food and water deprivation, space restriction, loud noise, strobe light, and intimidation with fake snakes. Huddling, self-clasping, locomotion and environmental exploration were monitored to evaluate behavioral changes. In addition, the window-opening test was used to evaluate the exploratory interest of the monkeys. The present results revealed that CUS-exposed monkeys displayed significant depression-like behaviors, including significant decreases in exploratory interest, locomotion, and exploration as well as significant increases in huddling and self-clasping behavior and the level of fecal cortisol after 8 weeks of CUS. Treatment with FLX (2.4 mg/kg, i. g.) or YL-0919 (1.2 mg/kg, i. g.) markedly reversed the depression-like behaviors caused by CUS, producing significant antidepressant effects. YL-0919 (once daily for 9 days) had a faster-onset antidepressant effect, compared with FLX (once daily for 17 days). In summary, the present study first established a CUS model using female cynomolgus monkeys with low social status and then successfully evaluated the onset time of 5-HTergic antidepressants. The results suggested that monkeys exposed to CUS displayed significant depression-like behaviors, and both FLX and YL-0919 produced antidepressant effects in this model. Moreover, YL-0919 appeared to act faster than FLX. The present study provides a promising prospect for the evaluation of fast-onset antidepressant drugs based on a CUS monkey model.

Prolonged deficits of associative motor learning in cynomolgus monkeys after long-term administration of phencyclidine.

Phencyclidine (PCP) is a potent drug of abuse that induces sustained schizophrenia-like symptoms in humans by blocking neurotransmission at N-methyl-d-aspartate (NMDA)-type glutamate receptors. Alterations in NMDA receptor function have been linked to numerous behavioral deficits and cognitive dysfunction. Classical eye-blink conditioning (EBC), including delay (dEBC) and trace (tEBC) paradigms, provides an effective means to study the neurobiology of associative motor learning in rodents, mammals and primates. To assess whether administration of low-dosage PCP for extended periods has prolonged effect to alter associative motor learning, in this study 19 adult cynomolgus monkeys were administered PCP (0.3mg/kg, intramuscularly) or saline twice a day for 14days. Twelve-fifteen months after PCP or saline injection, monkeys received dEBC, tEBC, or pseudo-paired training for 6 or 12 successive daily sessions, respectively. The results of this study show that percentage of conditioned response (CR) in dEBC increased as a function of training sessions in both PCP-treated and control monkeys and there was no significant CR% difference between the two groups. However, the CR timing in dEBC of PCP-treated monkeys was significantly impaired, as manifested by shorter CR peak latencies than those of the control group. PCP-treated animals showed significantly lower percentage of CR in tEBC compared to controls. PCP-treated animals were also more sensitive to outside stimuli in tEBC because the UR peak latency of PCP-treated group was significantly lower than the control group. These results indicated that cynomolgus monkeys manifested prolonged deficits in associative motor learning after long-term administration of phencyclidine.