The human renal lymphatics under normal and pathological conditions

Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S, Soh S & Ishii T (2006) Histopathology 49, 265–273 The human renal lymphatics under normal and pathological conditions AIMS: The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. METHODS AND RESULTS: Normal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney. CONCLUSIONS: Lymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics

Transgenic Rat Model of Neurodegeneration Caused by Mutation in the TDP Gene

TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43–related neurodegenerative diseases

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes