RESUMEN
Evidence suggests that the Parkinson's disease (PD) pathogenesis is strongly associated with bidirectional pathways in the microbiota-gut-brain axis (MGBA), and psychobiotics may inhibit PD progression. We previously reported that the novel psychobiotic strain, Lactobacillus plantarum PS128 (PS128), ameliorated abnormal behaviors and modulated neurotransmissions in dopaminergic pathways in rodent models. Here, we report that orally administering PS128 for 4 weeks significantly alleviated the motor deficits, elevation in corticosterone, nigrostriatal dopaminergic neuronal death, and striatal dopamine reduction in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. PS128 ingestion suppressed glial cell hyperactivation and increased norepinephrine and neurotrophic factors in the striatum of the PD-model mice. PS128 administration also attenuated MPTP-induced oxidative stress and neuroinflammation in the nigrostriatal pathway. Fecal analysis showed that PS128 modulated the gut microbiota. L. plantarum abundance was significantly increased along with methionine biosynthesis-related microbial modules. PS128 also suppressed the increased family Enterobacteriaceae and lipopolysaccharide and peptidoglycan biosynthesis-related microbial modules caused by MPTP. In conclude, PS128 ingestion alleviated MPTP-induced motor deficits and neurotoxicity.PS128 supplementation inhibited neurodegenerative processes in PD-model mice and may help prevent PD.
Asunto(s)
Lactobacillus plantarum , Fármacos Neuroprotectores , Enfermedad de Parkinson , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Enfermedad de Parkinson/tratamiento farmacológico , PirrolidinasRESUMEN
We previously reported a novel psychobiotic strain of Lactobacillus plantarum PS128 (PS128) which could ameliorate anxiety-like& depression-like behaviors and modulate cerebral dopamine (DA) and serotonin (5-HT) in mice. Here, we examine the possibility of using PS128 administration to improve tic-like behaviors by using a 5-HT2A and 5-HT2C receptor agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI). PS128 was orally administered to male Wistar rat for 2 weeks before two daily DOI injections. We recorded the behaviors immediately after the second DOI injection and compared the results with control and haloperidol treatment groups. PS128 significantly reduced tic-like behaviors and pre-pulse inhibition deficit in a threshold-dose of 109 CFU per day. Brain tissue analysis showed that DOI induced abnormal DA efflux in the striatum and prefrontal cortex, while PS128 ingestion improved DA metabolism and increased norepinephrine (NE) levels in these two regions. In addition, PS128 ingestion increased DA transporter and ß-arrestin expressions and decreased DOI-induced phosphorylation of DA and cAMP regulated phosphoprotein of molecular weight 32â¯kDa (DARPP-32) at Thr34 and extracellular regulated protein kinases (ERK). PS128 ingestion also modulated peripheral 5-HT levels and shaped the cecal microbiota composition, which helps to alleviate DOI-induced dysbiosis. These results suggested that PS128 ameliorated DOI-induced tic-like hyper-active behaviors via stabilizing cerebral dopaminergic pathways through its modulation of host's microbiota-gut-brain axis. Thus, we believe there are potentials for utilizing psychobiotics to improve syndromes caused by DA dysregulation in DA-related neurological disorders and movement disorders such as Tourette syndrome.
Asunto(s)
Lactobacillus plantarum/metabolismo , Tics/microbiología , Anfetaminas/farmacología , Animales , Encéfalo/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Microbioma Gastrointestinal/fisiología , Haloperidol/farmacología , Masculino , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar , Serotonina/metabolismo , Tics/inducido químicamenteRESUMEN
This four-week, randomized, double-blind, placebo-controlled study investigated the effects of Lactobacillus plantarum PS128 (PS128) on boys with autism spectrum disorder (ASD) aged 7-15 in Taiwan. All subjects fulfilled the criteria for ASD diagnosis of DSM-V and the Autism Diagnostic Interview-Revised (ADI-R). Questionnaires used for the primary outcome measure include the Autism Behavior Checklist-Taiwan version (ABC-T), the Social Responsiveness Scale (SRS) and the Child Behavior Checklist (CBCL). The Swanson, Nolan, and Pelham-IV-Taiwan version (SNAP-IV) and the Clinical Global Impression-improvement (CGI-I) were used for the secondary outcome measure. The results showed that PS128 ameliorated opposition/defiance behaviors, and that the total score of SNAP-IV for younger children (aged 712) improved significantly compared with the placebo group. Additionally, several elements were also notably improved in the PS128 group after 28-day consumption of PS128. Further studies are needed to better clarify the effects of PS128 for younger children with ASD on broader symptoms.
Asunto(s)
Trastorno del Espectro Autista/terapia , Lactobacillus plantarum , Probióticos/administración & dosificación , Adolescente , Factores de Edad , Trastorno del Espectro Autista/psicología , Niño , Conducta Infantil/fisiología , Método Doble Ciego , Humanos , Masculino , Placebos , Conducta Social , Encuestas y Cuestionarios , TaiwánRESUMEN
Emerging evidence indicates that ingestion of specific probiotics, known as "psychobiotics", confer beneficial effects on mental health. This study investigated antidepressant-like effects and possible underlying mechanisms of Lactobacillus paracasei PS23 (PS23), live or heat-killed, in a mouse model of corticosterone-induced depression using fluoxetine as standard drug. PS23 were orally gavaged to mice from day 1 to 41 or fluoxetine from day 17 to 41 and injected with corticosterone from day 17 to 37. After the last corticosterone treatment, anxiety- and depression-like behaviors were tested within 4â¯days. On day 42, serum and brain tissue were collected 24â¯min after forced swim stress. Abnormal behavioral changes induced by corticosterone were ameliorated by treatment with live PS23 in open field and sucrose preference tests, with heat-killed PS23 in open field, forced swim and sucrose preference tests, and with fluoxetine in open field and forced swim tests. Furthermore, both live and heat-killed PS23 and fluoxetine reversed corticosterone-reduced protein levels of brain-derived neurotropic factor, mineralocorticoid, and glucocorticoid receptors in the hippocampus. In addition, live PS23 also reverses corticosterone-reduced serotonin levels in hippocampus, prefrontal cortex and striatum; whereas heat-killed PS23 reverses corticosterone-reduced dopamine levels in hippocampus and prefrontal cortex. And fluoxetine normalized reduced corticosterone level in serum. These studies showed that both live and heat-killed PS23 can reverse chronic corticosterone-induced anxiety- and depression-like behaviors and that may provide insights into the mechanism and a potential psychobiotic for depression management.
Asunto(s)
Depresión/tratamiento farmacológico , Lacticaseibacillus paracasei/metabolismo , Probióticos/farmacología , Animales , Antidepresivos/farmacología , Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Corticosterona/análisis , Corticosterona/sangre , Trastorno Depresivo/tratamiento farmacológico , Modelos Animales de Enfermedad , Fluoxetina/farmacología , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Corteza Prefrontal/metabolismo , Receptores de Glucocorticoides/metabolismo , Estrés Psicológico/metabolismoRESUMEN
OBJECTIVE: To characterize hypertensive patients living in metropolitan cities in China. METHODS: This was a cross-sectional survey conducted in Beijing, Shanghai and Guangzhou. The eligibility criteria included outpatients 35-85 years of age with a systolic blood pressure (SBP) of ≥140 mmHg or a diastolic blood pressure (DBP) of ≥90 mmHg or both and/or patients receiving antihypertensive medications. The patients' demographic characteristics, medical history and findings of physical examinations, laboratory tests and cardiovascular imaging (i.e., ultrasonic cardiogram) were included in the survey. Risk stratification and the rate of hypertension control were evaluated. RESULTS: A total of 25,336 individuals were surveyed, of which 79.1% were from cardiology clinics and 51.8% were male hypertensives. The average SBP/DBP was 139.3±18.6/82.3±12.0 mmHg. The mean age was 63.6±11.5 years. The mean BMI was 25.1±3.8 kg/m(2). Among the men, 55.9% had a waist circumference of >90 cm. Among the women, 50.9% had a waist circumference of >85 cm. The percentages of patients with diabetes mellitus, heart disease and cerebral vascular disease were 20.3%, 39.2% and 10.4%, respectively. The smoking rate was 17.6%. Overall, 60.9% of the patients were in the very high risk group. While 97.7% of the patients were receiving antihypertensive drug therapy, only 40.2% had controlled SBP/DBP (i.e., under 140/90 mmHg). The control rate was statistically higher in Beijing and Shanghai than in Guangzhou and among older patients than among younger patients (43% among the patients >75 years of age vs. 28.1% among the patients 35-45 years of age). CONCLUSION: In Beijing, Shanghai and Guangzhou, most hypertensive patients have various cardiovascular risk factors and cardiovascular diseases. High blood pressure is not under appropriate control in all cases, especially among young hypertensives and patients living in Guangzhou city. Approaches designed to target multiple risk factors and concomitant cardiovascular diseases and boost the hypertension control rate are warranted.