RESUMEN
Perfluorooctane sulfonate (PFOS), an emerging environmental pollutant, is reported to cause neurotoxicity in animals and humans, but its underlying mechanisms are still unclear. We used in vivo models to investigate the effects of PFOS on cognition-related behaviors and related mechanisms. After 45 days of intragastric administration of PFOS (2 mg/kg or 8 mg/kg) in 7-week-old C57BL/6 mice, muscle strength, cognitive function and anxiety-like behavior were evaluated by a series of behavioral tests. The underling mechanisms of PFOS on impaired behaviors were evaluated by HE/Nissl staining, electron microscopy observation and western blot analysis. The results indicated that PFOS-exposed mice exhibited significant cognitive impairment, anxiety, neuronal degeneration and the abnormities of synaptic ultrastructure in the cortex and hippocampus. Western blot analysis indicated that PFOS exposure increased microtubule-associated protein light chain 3 (LC3) and decreased p62 protein levels, which may be associated with activation of autophagy leading to neuron damage. In summary, our results suggest that chronic exposure to PFOS adversely affects cognitive-related behavior in mice. These findings provide new mechanistic insights into PFOS-induced neurotoxicity.
Asunto(s)
Autofagia , Síndromes de Neurotoxicidad , Humanos , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Cognición , Proteínas Asociadas a MicrotúbulosRESUMEN
BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease and is featured by cognitive impairment. Procyanidins have been shown to have a potential protective effect against neurodegenerative diseases, but the underlying mechanism is not comprehensive enough. OBJECTIVE: To further investigate the effects of procyanidins from lotus seedpod (LSPC) on cognition in AD. METHODS: The APP/PS1 transgenic mice were administered with LSPC (100 mg/kg body weight) for five months. The Morris water maze test was used to assess learning and memory function, the long-term potentiation (LTP) was measured, and the expressions of Aß, pCREB/CREB and BDNF were quantified by western blot. RESULTS: LSPC significantly ameliorated cognitive dysfunction, reduced Aß deposition and reversed the remarkable reduction of the phosphorylation of CREB and the expression of BDNF, and then enhanced the effect of LTP in APP/PS1 mice. CONCLUSION: These results revealed that LSPC could ameliorate cognitive impairment through the CREB-BDNF pathway that mediates the enhancement of LTP in APP/PS1 transgenic mice.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Lotus , Enfermedades Neurodegenerativas , Proantocianidinas , Ratones , Animales , Ratones Transgénicos , Potenciación a Largo Plazo , Péptidos beta-Amiloides/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/farmacología , Proantocianidinas/farmacología , Proantocianidinas/uso terapéutico , Proantocianidinas/metabolismo , Lotus/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Semillas , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/farmacología , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , HipocampoRESUMEN
CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-inflammatory and antioxidative effects. OBJECTIVE: To explore the neuroprotective effect of SPJ on natural ageing of rat. MATERIALS AND METHODS: Sprague-Dawley (SD) rats 18-month-old were divided into ageing control, ageing treated with SPJ 10 or 30 mg/kg (n = 8). Five-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed or feed containing SPJ for 4 months. Cognitive level was evaluated by Morris water maze (MWM) test. The mechanisms of SPJ's neuroprotection were evaluated by transmission electron microscope, western blot analysis, and immunofluorescence in vivo and in vitro. RESULTS: SPJ attenuated ageing-induced cognitive impairment as indicated by elevated number of times crossing the target platform (from 1.63 to 3.5) and longer time spent in the target platform quadrant (from 1.33 to 1.98). Meanwhile, SPJ improved the morphology of microglia and synapse, and activated M2 microglia polarisation including increased hippocampus levels of CD206 (from 0.98 to 1.47) and YM-1 (from 0.67 to 1.1), and enhanced autophagy-related proteins LC3B (from 0.48 to 0.82), Beclin1 (from 0.32 to 0.51), Atg5 (from 0.22 to 0.89) whereas decreased p62 level (from 0.71 to 0.45) of ageing rats. In vitro study also showed that SPJ regulated the microglial polarisation and autophagy. DISCUSSION AND CONCLUSIONS: SPJ improved cognitive deficits of ageing rats through attenuating microglial inflammation and enhancing microglial autophagy, which could be used to treat neurodegenerative disorders.
