Basal lamina changes in neurodegenerative disorders

Background Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key pathological features of these disorders are blood-brain barrier (BBB) breakdown and protein aggregation. Main body The BBB is composed of various cell types and a non-cellular component---the basal lamina (BL). Although how different cells affect the BBB is well studied, the roles of the BL in BBB maintenance and function remain largely unknown. In addition, located in the perivascular space, the BL is also speculated to regulate protein clearance via the meningeal lymphatic/glymphatic system. Recent studies from our laboratory and others have shown that the BL actively regulates BBB integrity and meningeal lymphatic/glymphatic function in both physiological and pathological conditions, suggesting that it may play an important role in the pathogenesis and/or progression of neurodegenerative disorders. In this review, we focus on changes of the BL and its major components during aging and in neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). First, we introduce the vascular and lymphatic systems in the CNS. Next, we discuss the BL and its major components under homeostatic conditions, and summarize their changes during aging and in AD, PD, and ALS in both rodents and humans. The functional significance of these alterations and potential therapeutic targets are also reviewed. Finally, key challenges in the field and future directions are discussed. Conclusions Understanding BL changes and the functional significance of these changes in neurodegenerative disorders will fill the gap of knowledge in the field. Our goal is to provide a clear and concise review of the complex relationship between the BL and neurodegenerative disorders to stimulate new hypotheses and further research in this field.

The pericardium of Oikopleura dioica (Tunicata, Appendicularia) contains two distinct cell types and is rotated by 90 degrees to the left

The planktonic Oikopleura dioica belongs to Tunicata, the probable sister taxon to Craniota, and might show plesiomorphic characters, conserved from the common lineage of Tunicata and Craniota. In O. dioica a pericardium in a position similar to other chordates but also to the heart and pericardium of craniates is found. Surprisingly, little is known about the ultrastructure of the pericardium in O. dioica. Here, we show based on electron microscopy that the pericardium is completely lined by a single layer of 16 epithelial cells: 6 epithelial myocardial cells on the left side of the pericardium and 10 peritoneal cells constituting the right side. One of the peritoneal cells, situated at the ventral border between peritoneal cells and myocardial cells has an extension that anchors the pericardium to the basal lamina beneath the latero-ventral epidermis. The primary body cavity of O. dioica appears quite uniformly clear in electron microscopic aspect but several sheets, resembling the basal lamina of the pericardium cross the larger spaces of the body cavity and connect to the pericardial basal lamina. This is the first detailed description of two distinct cell types in the epithelial lining of the pericardium of O. dioica. In comparison with other chordates, we conclude that two cell types can be reconstructed for the last common ancestor of Chordata at least. The position of the pericardium at the intersection of trunk and tail in combination with the basal-lamina like sheets spanning the hemocoel is probably of importance for the function of the circulation of the hemocoelic fluid. Similar to the tail, the axis of the pericardium is shifted through 90 degrees to the left as compared to the main body axis of the trunk and we infer that this shift is an apomorphic character of Appendicularia.

Consequences of Microwave oven Exposed Diet on The Basal Lamina of Seminiferous Tubules of Mice

Usage of electronic gadgets like microwave oven is increasing day by day that heats the food by exposing it to electromagnetic radiations which has many hazardous effects on human health including fertility. Aim: To find the effects of microwave oven exposed diet on basal lamina of seminiferous tubules of mice alongwith protective effects of Mentha piperita and melatonin on the same tissue. Study Design: Randomized control trial. Methodology: Adult male mice (n=32) were divided into four groups. Control group (G1) received standard pellets prepared for mice. Second group (G2) was given mice pellets exposed to microwave oven. Third group (G3) received Mentha Piperita leaf extract along with mice pellets exposed to microwave oven and the fourth group (G4) received oral melatonin along with pellets exposed to microwave oven. Later their testicular tissue was removed for histological examination while basal lamina disruption was assessed by scoring. Data analyzed by SPSS 22.0v. Results: In group G2, there was slight disruption in the basal lamina in 75% of the cases while in experimental group G3, there was slight disruption of basal lamina only in 12.5% of the cases. However, in group G4, only 25% specimen had slight disruption of basal lamina Conclusion: It was concluded that microwave oven exposed diet produced severe disruption of basal lamina in group G2 that decreased in Mentha piperita and melatonin treated groups. However, Mentha piperita treated group produced better results than melatonin treated group. Keywords: Mice, Testis, Basal Lamina, Mentha piperita and Melatonin

Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor

Here, we report that important regulators of cilia formation and ciliary compartment–directed protein transport function in secretion polarity. Mutations in cilia genes cep290 and bbs2, involved in human ciliopathies, affect apical secretion of Cochlin, a major otolith component and a determinant of calcium carbonate crystallization form. We show that Cochlin, defective in human auditory and vestibular disorder, DFNA9, is secreted from small specialized regions of vestibular system epithelia. Cells of these regions secrete Cochlin both apically into the ear lumen and basally into the basal lamina. Basally secreted Cochlin diffuses along the basal surface of vestibular epithelia, while apically secreted Cochlin is incorporated into the otolith. Mutations in a subset of ciliopathy genes lead to defects in Cochlin apical secretion, causing abnormal otolith crystallization and behavioral defects. This study reveals a class of ciliary proteins that are important for the polarity of secretion and delineate a secretory pathway that regulates biomineralization.

M-Cadherin Is a PAX3 Target During Myotome Patterning

PAX3 belongs to the paired-homeobox family of transcription factors and plays a key role as an upstream regulator of muscle progenitor cells during embryonic development. Pax3-mutant embryos display impaired somite development, yet the consequences for myotome formation have not been characterized. The early myotome is formed by PAX3-expressing myogenic cells that delaminate from the dermomyotomal lips and migrate between the dermomyotome and sclerotome where they terminally differentiate. Here we show that in Pax3-mutant embryos, myotome formation is impaired, displays a defective basal lamina and the regionalization of the structural protein Desmin is lost. In addition, this phenotype is more severe in embryos combining Pax3-null and Pax3 dominant-negative alleles. We identify the adhesion molecule M-Cadherin as a PAX3 target gene, the expression of which is modulated in the myotome according to Pax3 gain- and loss-of-function alleles analyzed. Taken together, we identify M-Cadherin as a PAX3-target linked to the formation of the myotome.