Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in ...

The Physiology of Glucagon-like Peptide 1

Nerve terminals are specific sites of action of a very large number of toxins produced by many different organisms. The mechanism of action of three groups of presynaptic neurotoxins that interfere directly with the process of neurotransmitter release is reviewed, whereas presynaptic neurotoxins acting on ion channels are not dealt with here. These neurotoxins can be grouped in three large families: 1) the clostridial neurotoxins that act inside nerves and block neurotransmitter release via their metalloproteolytic activity directed specifically on SNARE proteins; 2) the snake presynaptic neurotoxins with phospholipase A(2) activity, whose site of action is still undefined and which induce the release of acethylcholine followed by impairment of synaptic functions; and 3) the excitatory latrotoxin-like neurotoxins that induce a massive release of neurotransmitter at peripheral and central synapses. Their modes of binding, sites of action, and biochemical activities are discussed in relation to the symptoms of the diseases they cause. The use of these toxins in cell biology and neuroscience is considered as well as the therapeutic utilization of the botulinum neurotoxins in human diseases characterized by hyperfunction of cholinergic terminals.

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.2.717

Neurotoxins Affecting Neuroexocytosis

https://www.jidonline.org/article/S0022-202X(15)41282-5/pdf

A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages.

The X-linked muscle-wasting disease Duchenne muscular dystrophy is caused by mutations in the gene encoding dystrophin. There is currently no effective treatment for the disease; however, the complex molecular pathology of this disorder is now being unravelled. Dystrophin is located at the muscle sarcolemma in a membrane-spanning protein complex that connects the cytoskeleton to the basal lamina. Mutations in many components of the dystrophin protein complex cause other forms of autosomally inherited muscular dystrophy, indicating the importance of this complex in normal muscle function. Although the precise function of dystrophin is unknown, the lack of protein causes membrane destabilization and the activation of multiple pathophysiological processes, many of which converge on alterations in intracellular calcium handling. Dystrophin is also the prototype of a family of dystrophin-related proteins, many of which are found in muscle. This family includes utrophin and α-dystrobrevin, which are involved in the maintenance of the neuromuscular junction architecture and in muscle homeostasis. New insights into the pathophysiology of dystrophic muscle, the identification of compensating proteins, and the discovery of new binding partners are paving the way for novel therapeutic strategies to treat this fatal muscle disease. This review discusses the role of the dystrophin complex and protein family in muscle and describes the physiological processes that are affected in Duchenne muscular dystrophy.

Function and genetics of dystrophin and dystrophin-related proteins in muscle

Electron-microscopic studies of two typical lesions of eccrine spiradenoma were performed to correlate ultrastructure and histopathology. The salient ultramorphological features of the parenchyma were an adenoid cystic organization composed of epithelial, myoepithelial, and nonepithelial cell types, and the presence of intracytoplasmic luminae within the epithelial cells. There were no indications that the parenchyma was secretorily active. The stroma ramified through the parenchyma, occupying extensive areas and forming tenuous septa of the loose connective tissue in which blood vessels and nerve fibers were embedded. Profiles of cystoid spaces resulting from invagination of stroma into the parenchyma were frequently encountered. Based on our observations, eccrine spiradenoma appears to differentiate toward ductal structures of eccrine sweat apparatus.

Eccrine spiradenoma. An electron microscopic study.

• A newly recognized disorder of black scalp hair is characterized by the irregularly alternating segmentation of hair into dark and light bands. A 15-year-old girl had segmented heterochromic scalp hair in association with iron-deficiency anemia. The clinical and laboratory investigations support the view that low serum iron levels play a critical role in reducing eumelanogenesis and in the possible failure of melanin transfer. The segmented heterochromic hair recovered completely after iron supplementation, which coincided with increased eumelanogenesis in the recovered hair. This clinical experience indicated participation of iron in the kinetics of melanogenesis within the follicular melanocytes. ( Arch Dermatol 1989;125:531-535)

Segmented Heterochromia in Black Scalp Hair Associated With Iron-Deficiency Anemia: Canities Segmentata Sideropaenica

To clarify the nature of the intracytoplasmic globules seen in the endothelial cells of the cutaneous angiomas of the Crow-Fukase syndrome, we performed light and electron microscopic as well as immunohistochemical studies. The proliferating plump endothelial cells of the angioma located in the mid-dermal portion contained numerous globules. IgG, A, M, and kappa and lambda light chain globulins were present in the endothelial cells containing these globules. Electron microscopy revealed osmiophilic fine fibrillar structures and amorphous substance in the globules. Thiery staining for detection of vicinal-glycol radicals of carbohydrate demonstrated the deposition of fine silver particles as a reaction product. We consider that the intracytoplasmic globules are phagolysosomes containing glycoprotein.

Kumiko Jitsukawa

Papers

Eccrine spiradenoma. An electron microscopic study.

Segmented Heterochromia in Black Scalp Hair Associated With Iron-Deficiency Anemia: Canities Segmentata Sideropaenica

Cutaneous angioma in Crow-Fukase syndrome: the nature of globules within the endothelial cells.