Apoptotic Factors and Mitochondrial Complexes Assist Determination of Strain-Specific Susceptibility of Mice to Parkinsonian Neurotoxin MPTP.

Identification of genetic mutations in Parkinson's disease (PD) promulgates the genetic nature of disease susceptibility. Resilience-associated genes being unknown till date, the normal genetic makeup of an individual may be determinative too. Our earlier studies comparing the substantia nigra (SN) and striatum of C57BL/6J, CD-1 mice, and their F1-crossbreds demonstrated the neuroprotective role of admixing against the neurotoxin MPTP. Furthermore, the differences in levels of mitochondrial fission/fusion proteins in the SN of parent strains imply effects on mitochondrial biogenesis. Our present investigations suggest that the baseline levels of apoptotic factors Bcl-2, Bax, and AIF differ across the three strains and are differentially altered in SN following MPTP administration. The reduction in complex-I levels exclusively in MPTP-injected C57BL/6J reiterates mitochondrial involvement in PD pathogenesis. The MPTP-induced increase in complex-IV, in the nigra of both parent strains, may be compensatory in nature. The ultrastructural evaluation showed fairly preserved mitochondria in the dopaminergic neurons of CD-1 and F1-crossbreds. However, in CD-1, the endoplasmic reticulum demonstrated distinct luminal enlargement, bordering onto ballooning, suggesting proteinopathy as a possible initial trigger.The increase in α-synuclein in the pars reticulata of crossbreds suggests a supportive role for this output nucleus in compensating for the lost function of pars compacta. Alternatively, since α-synuclein over-expression occurs in different brain regions in PD, the α-synuclein increase here may suggest a similar pathogenic outcome. Further understanding is required to resolve this biological contraption. Nevertheless, admixing reduces the risk to MPTP by favoring anti-apoptotic consequences. Similar neuroprotection may be envisaged in the admixed populace of Anglo-Indians.

Lack of IDH1 mutation in astroblastomas suggests putative origin from ependymoglial cells?

Astroblastomas are extremely rare neuroepithelial tumors of uncertain histogenesis, affecting children and young adults, and constitute a new addition to the WHO 2000 classification of CNS tumors. We report the largest series of nine cases diagnosed in a single institute over the last 13 years and review published literature. Mean age at presentation was 12.8 years (range: 22 months to 27years). Seven out of nine cases were supratentorial (frontal/frontoparietal - three, parieto-occipital - three, parafalcine - one), one was intraventricular and another was optochaismatic/suprasellar. Five cases were high grade (anaplastic) astroblastomas with Ki-67 labeling index of 8-10%. Immunohistochemical and ultrastructural evidence suggesting origin from cells intermediate between ependymocytes and astrocytes is presented. The histogenetic origin of these tumors remains speculative. But the lack of Isocitrate dehydrogenase 1 (IDH1) mutation as detected by immunohistochemistry in this study, which is similar to ependymomas supports putative origin from ependymoglial cells. Out of the nine cases, recurrence was noted in one case, 12 months after gross total resection with progression to high grade in the recurrent tumor. There is no recommended treatment protocol due to the rarity of this entity and prognostic factors are yet to be established.

Fabry's disease: An ultrastructural study of nerve biopsy.

Fabry's disease, an X linked recessive disorder caused by the deficiency of alpha-galactosidase A (alpha-gal A), leads to progressive accumulation of glycosphingolipids. We report this rare disease in a 19-year-old boy who presented with angiokeratomas, paresthesia and corneal opacities, and nerve biopsy revealed by electron microscopy lamellated inclusions in the smooth muscle, perineurial and endothelial cells characteristic of Fabry's disease.

Localization of ferrochelatase in Plasmodium falciparum.

Our previous studies have demonstrated de novo haem biosynthesis in the malarial parasite (Plasmodium falciparum and P. berghei). It has also been shown that the first enzyme of the pathway is the parasite genome-coded ALA (delta-aminolaevulinate) synthase localized in the parasite mitochondrion, whereas the second enzyme, ALAD (ALA dehydratase), is accounted for by two species: one species imported from the host red blood cell into the parasite cytosol and another parasite genome-coded species in the apicoplast. In the present study, specific antibodies have been raised to PfFC (parasite genome-coded ferrochelatase), the terminal enzyme of the haem-biosynthetic pathway, using recombinant truncated protein. With the use of these antibodies as well as those against the hFC (host red cell ferrochelatase) and other marker proteins, immunofluorescence studies were performed. The results reveal that P. falciparum in culture manifests a broad distribution of hFC and a localized distribution of PfFC in the parasite. However, PfFC is not localized to the parasite mitochondrion. Immunoelectron-microscopy studies reveal that PfFC is indeed localized to the apicoplast, whereas hFC is distributed in the parasite cytoplasm. These results on the localization of PfFC are unexpected and are at variance with theoretical predictions based on leader sequence analysis. Biochemical studies using the parasite cytosolic and organellar fractions reveal that the cytosol containing hFC accounts for 80% of FC enzymic activity, whereas the organellar fraction containing PfFC accounts for the remaining 20%. Interestingly, both the isolated cytosolic and organellar fractions are capable of independent haem synthesis in vitro from [4-14C]ALA, with the cytosol being three times more efficient compared with the organellar fraction. With [2-14C]glycine, most of the haem is synthesized in the organellar fraction. Thus haem is synthesized in two independent compartments: in the cytosol, using the imported host enzymes, and in the organellar fractions, using the parasite genome-coded enzymes.

Light microscopical and ultrastructural studies on the vas deferens of the lizard Mabuya carinata.

Adult male lizards (Mabuya carinata) were studied during breeding and non breeding seasons to determine the regional and seasonal differences if any in the vas deferens and to compare ultrastructural features of luminal epithelial cells with those of endotherms. The vas deferens of the lizard is a convoluted tube extending from the epididymis to the hemipenis passing over the kidney. Based on morphometric data of luminal diameter and epithelial cell height three distinct regions viz; proximal, middle and distal regions were identified in the vas deferens. The epithelium is surrounded by a thin layer of lamina propria, many layers of circular smooth muscle fibers and an outer layer of visceral pleuro peritoneum. Based on cell and nuclear morphology and ultrastructure, five different cell types viz; principal cell, basal cell, mitochondria rich cell, halo cell and narrow cell were identified in the epithelium during both breeding and non breeding season. Principal cells and basal cells were more abundant in both seasons. The types of luminal epithelial cells of vas deferens of M. carinata and their ultrastructural features are similar to those of mammals. Further, vas deferens of M. carinata differs from mammals in having only circular smooth muscles in contrast to circular and longitudinal muscles of mammalian vas deferens. To the best of our knowledge this is the first report describing cell types of vas deferens, their ultrastructure and ultrastructural seasonal variations in reptiles.