The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson's disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples from patients with confirmed PD and Thy1-αSyn mice were analyzed using 16S ribosomal RNA sequencing. Compared to healthy controls, the relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients. In mice, the abundance of Gammaproteobacteria was negligible in both Thy1-αSyn and wild-type (WT) animals, while Verrucomicrobiae were reduced in Thy1-αSyn mice. The effect of LPS on intestinal barrier function was investigated in vitro using intestinal epithelial (IEC-6) cells, and in vivo via administration of LPS in drinking water to Thy1-αSyn mice. Acute exposure to LPS in vitro resulted in a reduction and altered distribution of the tight junction markers ZO-1 and e-Cadherin around the cell membrane in IEC-6 cells, as shown by immunohistochemistry. LPS administration in Thy1-αSyn mice resulted in the emergence of early motor manifestations at 10 weeks, compared to untreated mice who were still asymptomatic at this age. This study reaffirms that an altered microbiome exists in patients with PD, and supports the notion of a proinflammatory gut microbiome environment as a trigger for PD pathogenesis.

Background Cognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated. Objectives This cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort. Methods Cognitive function was evaluated using the Addenbrooke’s Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson’s Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates. Results Cross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia. Conclusions Sex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.

We have previously demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties, with poly-arginine peptide R18 identified as being highly effective at reducing infarct volume following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. Since peptides synthesised using D-isoform amino acids have greater stability than L-isoform peptides due to increased resistance to proteolytic degradation, they represent potentially more effective peptide therapeutics. Therefore we compared the neuroprotective efficacy of R18 and its D-enantiomer R18D following permanent MCAO in the Wistar rat. Furthermore, as increased peptide stability may also increase peptide toxicity, we examined the effects of R18 and R18D on cultured cortical neurons, astrocytes, brain endothelial cells (bEND.3), and embryonic kidney cells (HEK293) following a 10-minute or 24-hour peptide exposure duration. The in vivo studies demonstrated that R18D resulted in a greater reduction in mean infarct volume compared to R18 (33%, p = 0.004 vs 12%, p = 0.27) after intravenous administration at 300 nmol/kg 30 minutes after MCAO. Both R18D and R18 reduced cerebral hemisphere swelling to a comparable degree (27%, p = 0.03 and 30%, p = 0.02), and improved neurological assessment scores (1.5, p = 0.02 and 2, p = 0.058 vs 3 for vehicle). No abnormal histological findings specific to peptide treatments were observed in hematoxylin and eosin stained sections of kidney, liver, spleen, lung and heart. In vitro studies demonstrated that R18 and R18D were most toxic to neurons, followed by astrocytes, HEK293 and bEND.3 cells, but only at high concentrations and/or following 24-hour exposure. These findings further highlight the neuroprotective properties of poly-arginine peptides, and indicate that R18D at the dose examined is more potent than R18 in Wistar rats, and justify continued investigation of the R18 peptide as a novel neuroprotective agent for stroke.

BackgroundWhile constipation is a well‐known non‐motor symptom which may precede the onset of the classical motor symptoms of PD, there have been few comprehensive studies of gastrointestinal (GI) symptoms in people with PD (PwP).ObjectivesTo investigate the spectrum of GI symptoms in an Australian PwP cohort and their relationship to use of anti‐parkinsonian medications dietary habits and smoking.MethodsThe prevalence and severity of GI symptoms were compared in a group of 163 PwP and 113 healthy control subjects using the Gastrointestinal Symptom Rating Scale (GSRS). Corrected linear regression models were used to determine differences between PwP and controls, and to investigate the influence of different classes of anti‐Parkinsonian medications.ResultsPwP reported a greater frequency of constipation and GI‐associated illnesses when compared to healthy controls. Total GSRS scores (P < 0.0001), upper GI symptoms (P < 0.0001), and hypoactive GI Symptoms (P < 0.0001) were all significantly greater in the PD cohort than controls. Further analyses revealed a positive association between the use of anti‐Parkinsonian medications and total GSRS scores (P < 0.001), as well as upper GI symptoms (P < 0.001) and hypoactive GI function (P < 0.001).ConclusionsThis study illustrates the frequency and array of GI symptoms in a large PD cohort. The findings indicate that anti‐parkinsonian medications play an important role in the presentation and development of GI symptoms.

Background. Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson’s disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods. Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson’s disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. Results. People with Parkinson’s disease displayed significantly elevated homocysteine levels (p<0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson’s disease (rs = 0.319, p<0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson’s disease (rs = −0.449, p<0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRS III score in male patients (p=0.004) and predictive of total ACE-R score in female patients (p=0.021). Conclusion. Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson’s disease and poorer cognitive performance in females with Parkinson’s disease. Our gender-specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD.

Background Impulsive behaviour has become increasingly recognised as a neuropsychiatric complication of Parkinson's disease (PD). Thought to be a product of compromised cognitive control, the spectrum of impulsive behaviours in PD ranges from cognitive disinhibition to impulse control disorders (ICDs). Objective At present, there are no indicators for trait impulsivity in PD. The objective of the current study was to identify demographic and clinical predictors of susceptibility to trait impulsivity in a cohort of PD patients. Methods The current study assessed impulsivity using the Barratt Impulsiveness Scale 11 (BIS-11) in a cohort of 87 PD patients. General linear models (GLMs) were used to identify clinical and demographic variables predictive of heightened BIS-11 second-order attentional and nonplanning subscale scores. Results Male gender, no history of smoking, postsecondary education, and heightened disease severity were predictive of increased BIS-11 attentional scores (p < 0.05). Similarly, male gender, after secondary education, and disease severity were predictive of increased BIS-11 nonplanning scores (p < 0.05). Contrary to previous reports, dopaminergic medication use was not a significant determinant of either BIS-11 subscale scores. Conclusions Several demographic and clinical variables including male gender, no history of past smoking, after secondary education, and elevated disease severity are associated with impulsivity in PD.

Since the first case of the novel coronavirus emerged in late 2019 (COVID-19), it quickly spread beyond China, with reported cases in nearly all countries and territories. As these unprecedented times have resulted in significant social and economic disruption, educational institutions have been forced to implement alternative teaching and learning approaches, including a total transition to online learning. Given the dependence of undergraduate science units and degrees on practical and laboratory activities, students and academics are faced with significant hurdles regarding delivery, learning, and assessment. Therefore, this article considers the impact of COVID-19 and the approaches being utilized to facilitate undergraduate science learning during the evolving pandemic.

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