Effect of Solanum surattense seed on the oxidative potential of cauda epididymal spermatozoa

Objective

To evaluate the effect of aqueous seed extract of Solanum surattense (S. surattense) on the oxidative potential of cauda epididymal spermatozoa.

Methods

S. surattense seed extract was orally administered at the dosage of 10 mg/kg b.w. for 15 days, after which aspartate transferase (AST), alanine transferase (ALT), glutamate dehydrogenase (GDH), citric acid and iso-citrate dehydrogenase (ICDH) were assayed.

Results

The activity levels of the enzymes AST and ALT, which are considered to be the androgenicity in the sperm suspension, were depleted in the extract fed rats. The activity level of the enzyme ICDH, was reduced significantly in the treated group (P<0.001).

Conclusions

It can be concluded that the oral administration of the aqueous seed extract of S. surattense can deplete the oxidative stress of cauda epididymal spermatozoa in albino rats.     

Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.     

Pathogenicity of exonic indels in fused in sarcoma in amyotrophic lateral sclerosis

Insertion and deletion variants (indels) within poly glycine tracts of fused in sarcoma (FUS) were initially reported as causative of disease in amyotrophic lateral sclerosis (ALS). Subsequent studies identified similar indels in controls and suggested that these indels may confer susceptibility to ALS. We aimed to elucidate the role of previously published and novel exonic indels in FUS in an extensive cohort of 630 ALS patients and 1063 controls. We detected indels in FUS exons 5, 6, 12, and 14 with similar frequencies in patients (0.95%) and controls (0.75%). Exonic indels in poly glycine tracts were also observed with similar frequencies. The largest indel (p.Gly138_Tyr143del) was observed in 1 control. In 1 patient, a 3 base pair deletion in exon 14 (p.Gly475del) was identified, however in vitro studies did not reveal abnormal localization of p.Gly475del mutant FUS. These findings suggest that not all exonic indels in FUS cause disease.     

First neuropathological description of a patient with Parkinson's disease and LRRK2 p.N1437H mutation

The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson's disease (PD). So far, only two families worldwide have been identified with this mutation. By screening DNA from seven brains of PD patients, we found one individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically, the patient had levodopa-responsive PD with tremor, and developed severe motor fluctuations during a disease duration of 19 years. There was severe and painful ON-dystonia, and severe depression with suicidal thoughts during OFF. In the advanced stage, cognition was slow during motor OFF, but there was no noticeable cognitive decline. There were no signs of autonomic nervous system dysfunction. Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory results on motor symptoms. The patient committed suicide. Neuropathological examination revealed marked cell loss and moderate alpha-synuclein positive Lewy body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A striking finding was very pronounced ubiquitin-positive pathology in the brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most pronounced in the white matter, and was out of proportion to the comparatively weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly positive, revealing non-specific changes, but staining for TDP-43 and FUS was entirely negative. The distribution and shape of ubiquitin-positive lesions in this patient differed from the few previously described patients with LRRK2 mutations and ubiquitin pathology, and the ubiquitinated protein substrate remains undefined.     

Crohn’s and Parkinson’s Disease-Associated LRRK2 Mutations Alter Type II Interferon Responses in Human CD14+ Blood Monocytes Ex Vivo

Journal of Neuroimmune Pharmacology - The Leucine Rich Repeat Kinase 2 (LRRK2) is one of causative genes of familial Parkinson’s disease (PD). The M2397T polymorphism in LRRK2 is genetically...     

Maternal occupational exposure and congenital heart defects in offspring

Objectives:Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD.Methods:For this case–control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix.Results:An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (OR_adj) 1.90, 95% confidence interval (CI) 1.01–3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (OR_adj 2.68, 95% CI 1.07–6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (OR_adj 2.94, 95% CI 1.21–7.13) and pulmonary valve stenosis (OR_adj 1.99, 95% CI 1.10–3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (OR_adj 2.40, 95% CI 1.09–5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (OR_adj 3.23, 95% CI 1.14–9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (OR_adj 0.32, 95% CI 0.11–0.94).Conclusions:Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development.     

Rapidly progressive autosomal dominant Parkinsonism and dementia with Pallido-Ponto-Nigral Gegeneration (PPND) and Disinhibition-Dementia-Parkinsonism-Amyotrophy Complex (DDPAC) are clinically distinct conditions that are both linked to 17q21-22

Genetic analysis provides specific etiologic information about disease that cannot be deduced by clinical and pathologic investigations alone. Two large families have been characterized with multi-system degeneration: rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration (PPND) and disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC). Linkage analysis identified a locus, wld, on-17q21-22 that is responsible for DDPAC. Analysis of a PPND family shows that PPND is also due to a gene on 17q21-22. Comparison of genealogic, clinical, diagnostic, and pathologic data shows that DDPAC and PPND are distinct disorders suggesting two different mutations in wld. Literature review identifies many kindreds with multi-system degeneration that may be allelic.     

German-Canadian family (family A) with parkinsonism, amyotrophy, and dementia - Longitudinal observations

Etiology of Parkinson's disease (PD), amyotrophy lateral sclerosis (ALS), and Alzheimer's disease (AD) remains uncertain. Environmental factors probably play a role, but genetic influences may predispose certain individuals to develop each of these major neurodegenerative disorders. We describe our longitudinal observations concerning a Canadian family traced to Northern Germany. Autosornal dominant inheritance has been established. Affected members present with L-dopa responsive parkinsonism and amyotrophy. In the German portion of the family some individuals displayed only dementia or focal dystonia. Linkage analysis studies performed with polymorphic markers associated with 13 candidate genes provided no significant evidence for linkage with any of the genes examined. Positron emission tomography with [(18)F]-6-fluoro-L-dopa (FD) and [su11C]-raclopride (raclopride) of one affected subject revealed reduced striatal FD uptake particularly in putamen, and an increased raclopride striatum/background ratio. Postmortem levels of dopamine and its metabolites were greatly reduced in caudate and putamen of two patients. There was substantial neuronal loss in the substantia nigra and the presence of abundant eosinophilic granules (different than Lewy bodies) in surviving neurons. One of them also showed mild loss of anterior horn cells, while another showed abundant senile plaques and some neurofibrillary tangles in distribution and intensity typical of mild to moderate AD. Our report further describes this unique family with a combination of clinical features of PD, ALS, and AD. By studying kindreds like this we may learn more about the pathophysiology of sporadic forms of PD, ALS, or even AD.