Complement peptides and neuronal dysfunction in the central nervous system: Specificity of receptor sites for anaphylatoxin C3a activity in the rat hypothalamus

1988 ◽  
Vol 15 (2-3) ◽  
pp. 175-187 ◽  
Author(s):  
Curtis A. Williams ◽  
Nicole Schupf ◽  
Christopher L. Reilly ◽  
Jolynn Wagner
2017 ◽  
Vol 114 (44) ◽  
pp. E9318-E9327 ◽  
Author(s):  
Sudhir K. Yadav ◽  
Sridhar Boppana ◽  
Naoko Ito ◽  
John E. Mindur ◽  
Martin T. Mathay ◽  
...  

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) mainly in young adults, and a breakage of immune tolerance to CNS self-antigens has been suggested to initiate CNS autoimmunity. Age and microbial infection are well-known factors involved in the development of autoimmune diseases, including MS. Recent studies have suggested that alterations in the gut microbiota, referred to as dysbiosis, are associated with MS. However, it is still largely unknown how gut dysbiosis affects the onset and progression of CNS autoimmunity. In this study, we investigated the effects of age and gut dysbiosis on the development of CNS autoimmunity in humanized transgenic mice expressing the MS-associated MHC class II (MHC-II) gene, HLA-DR2a, and T-cell receptor (TCR) genes specific for MBP87-99/DR2a that were derived from an MS patient. We show here that the induction of gut dysbiosis triggers the development of spontaneous experimental autoimmune encephalomyelitis (EAE) during adolescence and early young adulthood, while an increase in immunological tolerance with aging suppresses disease onset after late young adulthood in mice. Furthermore, gut dysbiosis induces the expression of complement C3 and production of the anaphylatoxin C3a, and down-regulates the expression of the Foxp3 gene and anergy-related E3 ubiquitin ligase genes. Consequently, gut dysbiosis was able to trigger the development of encephalitogenic T cells and promote the induction of EAE during the age window of young adulthood.


2018 ◽  
Vol 9 (3) ◽  
pp. 417-425 ◽  
Author(s):  
T. G. Turitskaya ◽  
S. N. Lukashev ◽  
V. P. Lyashenko ◽  
G. G. Sidorenko

One of the factors of the environment which essentially shifts homeostasis is diets which contain caffeine. The aim of the study was to find out the basic characteristics of background electrical activity of trophotrophic and ergotrophic zones of the hypothalamus in conditions of chronic caffeine alimentation. Experiments were carried out on non-linear white male rats. The first group consisted of control animals (n = 22). The second group (n = 24) was represented by the animals that were given pure caffeine in an amount of 150 mg/kg/day with their meal. The registration on a electrohypothalamogram was carried out in conditions of acute experiment, every 2 weeks for 12 weeks. The spectral (mkV2) and the normalized power (%) of electrohypothalamogram waves were analyzed within the common frequency band. The analysis of the results allowed us to establish a certain specificity of the reaction of the neuronal system of the trophotropic and ergotropic zones of the rat hypothalamus to the effect of chronic caffeine alimentation. The main difference in the reactive state of electrophysiological indices in the trophotrophic zone of rats is the lack of a typical desynchronization from the 4th to the 8th week of the study and the hypersynchronization after 12 weeks of the experiment. The most probable mechanism that explains the results obtained is the ultra-powerful GABA-ergic modulation of this zone, the main energy-accumulating center. Perhaps, this powerful inhibitory resource in this cerebral locus is the main stress-limiting factor that makes this zone of the central nervous system of rats less sensitive to caffeine exposure. Instead, under the influence of chronic caffeine load in the ergotropic zone of the hypothalamus, after 6 weeks of the experiment desynchronous high-frequency rhythms dominated. During the subsequent time of the experiment, we observed a decrease in both low-frequency and high-frequency components of the electrohypothalamogram of this zone. This gives reason to assume that the key component of the neurophysiological response of the posterior hypothalamus of rats to the caffeine ration is the powerful glutamatergic effects on the pre-synaptic and post-synaptic neurons under conditions of reactive exhaustion of local neurosynthetics. Caffeine depletion of the hypothalamic neurotransmission at the end of the experiment is replaced by an effective adaptive ergotropic restoration of neurosynthetic activity in this locus of the central nervous system of rats. Thus, caffeine has a powerful activating effect on the ergotropic function of the posterior hypothalamus of rats. Such a difference in the chronic effect of caffeine on the trophotropic and ergotropic zone of the rat hypothalamus is primarily due to the different mediator support of these zones underlying their physiological purpose. GABA is the main mediator of the trophotropic zone and the main neurotransmitter of its synchronous activity. At the same time, neurotransmitter support of the ergotropic zone is represented by glutamate, which, along with other agents, implements its desynchronous activity. Since caffeine stimulates excitation, activating the pathways traditionally associated with motivational and motor reactions in the brain, it can be assumed that this explains the fact of a more powerful influence of caffeine precisely on the ergotrophic zone of the hypothalamus.


Author(s):  
Gladys Harrison

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.


Author(s):  
John L.Beggs ◽  
John D. Waggener ◽  
Wanda Miller ◽  
Jane Watkins

Studies using mesenteric and ear chamber preparations have shown that interendothelial junctions provide the route for neutrophil emigration during inflammation. The term emigration refers to the passage of white blood cells across the endothelium from the vascular lumen. Although the precise pathway of transendo- thelial emigration in the central nervous system (CNS) has not been resolved, the presence of different physiological and morphological (tight junctions) properties of CNS endothelium may dictate alternate emigration pathways.To study neutrophil emigration in the CNS, we induced meningitis in guinea pigs by intracisternal injection of E. coli bacteria.In this model, leptomeningeal inflammation is well developed by 3 hr. After 3 1/2 hr, animals were sacrificed by arterial perfusion with 3% phosphate buffered glutaraldehyde. Tissues from brain and spinal cord were post-fixed in 1% osmium tetroxide, dehydrated in alcohols and propylene oxide, and embedded in Epon. Thin serial sections were cut with diamond knives and examined in a Philips 300 electron microscope.


Author(s):  
Ezzatollah Keyhani

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.


Author(s):  
S.S. Spicer ◽  
B.A. Schulte

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.


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