scholarly journals Lack of Cathepsin D in the Central Nervous System Results in Microglia and Astrocyte Activation and the Accumulation of Proteinopathy-related Proteins

2021 ◽  
Author(s):  
Chigure Suzuki ◽  
Junji Yamaguchi ◽  
Takahito Sanada ◽  
Juan Alejandro Oliva Trejo ◽  
Souichirou Kakuta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cathepsin D ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Whole Body ◽  
Intestinal Necrosis ◽  
Ceroid Lipofuscinosis ◽  
Associated Proteins ◽  
The Central Nervous System ◽  
Related Proteins

Abstract Neuronal ceroid lipofuscinosis is one of many neurodegenerative storage diseases characterized by excessive accumulation of lipofuscins. CLN10 disease, an early infantile neuronal ceroid lipofuscinosis, is associated with a gene that encodes cathepsin D (CtsD), one of the major lysosomal proteases. Whole body CtsD-knockout mice show neurodegenerative phenotypes with the accumulation of lipofuscins in the brain and also show defects in other tissues including intestinal necrosis. To clarify the precise role of CtsD in the central nervous system (CNS), we generated a CNS-specific CtsD-knockout mouse (CtsD-CKO). CtsD-CKO mice were born normally but developed seizures and their growth stunted at around postnatal day 23±1. CtsD-CKO did not exhibit apparent intestinal symptoms as those observed in whole body knockout. Histologically, autofluorescent materials were detected in several areas of the CtsD-CKO mouse’s brain, including: thalamus, cerebral cortex, hippocampus, and cerebellum. Expression of ubiquitin and autophagy-associated proteins was also increased, suggesting that the autophagy-lysosome system was impaired. Microglia and astrocytes were activated in the CtsD-CKO thalamus, and Inducible nitric oxide synthase (iNOS), an inflammation marker, was increased in the microglia. Interestingly, deposits of proteinopathy-related proteins, phosphorylated α-synuclein and Tau protein, were also increased in the thalamus of CtsD-CKO infant mice. Considering these results, it is likely that the CtsD-CKO mouse is a useful mouse model to investigate the contribution of cathepsin D to the early phases of neurodegenerative diseases in relation to lipofuscins, proteinopathy-related proteins and activation of microglia and astrocytes.

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

scholarly journals Region-specific irradiation system with heavy-ion microbeam for active individuals of Caenorhabditis elegans

2017 ◽  
Vol 58 (6) ◽  
pp. 881-886 ◽  
Author(s):  
Michiyo Suzuki ◽  
Yuya Hattori ◽  
Tetsuya Sakashita ◽  
Yuichiro Yokota ◽  
Yasuhiko Kobayashi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Microfluidic Channel ◽  
Muscle Cells ◽  
Heavy Ion ◽  
Whole Body ◽  
Carbon Ions ◽  
Tail Region ◽  
The Central Nervous System

Abstract Radiation may affect essential functions and behaviors such as locomotion, feeding, learning and memory. Although whole-body irradiation has been shown to reduce motility in the nematode Caenorhabditis elegans, the detailed mechanism responsible for this effect remains unknown. Targeted irradiation of the nerve ring responsible for sensory integration and information processing would allow us to determine whether the reduction of motility following whole-body irradiation reflects effects on the central nervous system or on the muscle cells themselves. We therefore addressed this issue using a collimating microbeam system. However, radiation targeting requires the animal to be immobilized, and previous studies have anesthetized animals to prevent their movement, thus making it impossible to assess their locomotion immediately after irradiation. We developed a method in which the animal was enclosed in a straight, microfluidic channel in a polydimethylsiloxane chip to inhibit free motion during irradiation, thus allowing locomotion to be observed immediately after irradiation. The head region (including the central nervous system), mid region around the intestine and uterus, and tail region were targeted independently. Each region was irradiated with 12 000 carbon ions (12C; 18.3 MeV/u; linear energy transfer = 106.4 keV/μm), corresponding to 500 Gy at a φ20 μm region. Motility was significantly decreased by whole-body irradiation, but not by irradiation of any of the individual regions, including the central nervous system. This suggests that radiation inhibits locomotion by a whole-body mechanism, potentially involving motoneurons and/or body-wall muscle cells, rather than affecting motor control via the central nervous system and the stimulation response.

I. Environmental Contamination and Biochemical Relationships

1975 ◽  
Vol 38 (5) ◽  
pp. 285-300 ◽  
Author(s):  
A. G. HUGUNIN ◽  
R. L. BRADLEY
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Methyl Mercury ◽  
Sea Water ◽  
Inorganic Mercury ◽  
Whole Body ◽  
Irreversible Damage ◽  
Mercury Compounds ◽  
The Central Nervous System ◽  
Pass Through

Mercury is naturally concentrated in geographical belts, but geological cycling has distributed the element in all strata of the earth. Natural concentrations of mercury are approximately 100 ppb in soil, 0.06 ppb in fresh water, 0.01–0.30 ppb in sea water, and 0.003–0.009 μg/m3 in air. Concentrations vary, being highest near mineral deposits. The concentration of mercury in some areas has been significantly increased by human carelessness. An epidemic among Japanese fishing families, death of Swedish wildlife, and discovery of elevated mercury levels in American fish focused attention on this problem. The discovery that certain species are capable of methylating inorganic mercury indicates pollution with any chemical form of mercury is dangerous. Alkylmercurials are the most dangerous form of mercury in the environment. Alkylmercurials are absorbed from the gastrointestinal tract, diffuse across the blood-brain carrier, and pass through the placental membrane in significantly higher proportions than other mercury compounds. The whole body half-life of methyl mercury in humans is 76 ± 3 days compared to half-lives of 37 ± 3 days for men and 48 ± 5 days for women observed for mercuric salts. Not readily broken down, sufficient concentrations of methyl mercury can cause irreversible damage to the central nervous system. Renal damage usually results from high levels of aryl- or alkoxyalkylmercurials and inorganic mercury; however, vapors of elemented mercury can damage the central nervous system. Organic mercury compounds cause chromosome changes, but the medical implications resulting from levels of mercury in food are unknown. The concentration of mercury in red blood cells and hair is indicative of the exposure to alkylmercurials. On a group basis, blood and urine concentrations of mercury may corrrelate with recent exposure to mercury.

Sign in / Sign up

Export Citation Format

Share Document