Deletion of muscarinic type 1 acetylcholine receptors alters splenic lymphocyte functions and splenic noradrenaline concentration

2015 ◽  
Vol 29 (1) ◽  
pp. 135-142 ◽  
Author(s):  
Susanne Hainke ◽  
Johannes Wildmann ◽  
Adriana del Rey
2018 ◽  
Author(s):  
Julia C. Lemos ◽  
Jung Hoon Shin ◽  
Anna E. Ingebretson ◽  
Lauren K. Dobbs ◽  
Veronica A. Alvarez

AbstractAcute stressors can stimulate appetitive and exploratory behaviors, not just produce negative affect that impair performance. Corticotropin releasing factor (CRF), which is released in the brain in response to stress, acts on different targets and circuits to mediate both the negative and positive effects of stress. In the nucleus accumbens, CRF facilitates appetitive behavior through mechanisms not fully understood. Here we report that cholinergic interneurons (CINs) are a novel target for CRF actions in the striatum. CRF enhances the spontaneous firing via activation of CRF-type 1 receptors expressed on CINs. This causes the activation muscarinic acetylcholine receptors type 5, which mediate CRF potentiation of dopamine transmission in the striatum. Repeated stress selectively dampens some CRF functions but spare effect on CINs and changes CRF-R1 expression in a cell-specific manner. These data highlight the existence of diverse CRF targets within the striatum, which vary in their resilience to stress.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2528
Author(s):  
Ilenia Martinelli ◽  
Daniele Tomassoni ◽  
Proshanta Roy ◽  
Francesco Amenta ◽  
Seyed Khosrow Tayebati

The association between obesity and loss of cognitive performance has been recognized. Although there are data regarding the metabolic alterations in obese conditions and the development of neuroinflammation, no clear evidence concerning obesity-related cholinergic and synaptic impairments in the frontal cortex and hippocampus has been reported yet. Here, we investigate different cholinergic and synaptic markers in 12-, 16-, and 20-week-old obese Zucker rats (OZRs) compared with lean littermate rats (LZRs), using immunochemical and immunohistochemical analysis. Consequently, OZRs showed body weight gain, hypertension, and dysmetabolism. In 20-week-old OZRs, the reduction of vesicular acetylcholine transporter (VAChT) and alpha7 nicotinic acetylcholine receptors (α7nAChR) occurred both in the frontal cortex and in the hippocampus, suggesting a cognitive dysfunction due to obesity and aging. Among the muscarinic receptors analyzed, the level of expression of type 1 (mAChR1) was lower in the hippocampus of the older OZRs. Finally, we showed synaptic dysfunctions in OZRs, with a reduction of synaptophysin (SYP) and synaptic vesicle glycoprotein 2B (SV2B) in 20-week-old OZRs, both in the frontal cortex and in the hippocampus. Taken together, our data suggest specific alterations of cholinergic and synaptic markers that can be targeted to prevent cognitive deficits related to obesity and aging.


2006 ◽  
Vol 96 (5) ◽  
pp. 2501-2512 ◽  
Author(s):  
Mackenzie E. Hofmann ◽  
Ben Nahir ◽  
Charles J. Frazier

Hilar mossy cells represent a unique population of local circuit neurons in the hippocampus and dentate gyrus. Here we use electrophysiological techniques in acute preparations of hippocampal slices to demonstrate that depolarization of a single hilar mossy cell can produce robust inhibition of local GABAergic afferents. This depolarization-induced suppression of inhibition (DSI) can be observed as a transient reduction in frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) or as a transient reduction in amplitude of evoked IPSCs (eIPSCs). We find that DSI of eIPSCs as observed in hilar mossy cells is enhanced by activation of muscarinic acetylcholine receptors, blocked by chelation of postsynaptic calcium, and critically dependent on retrograde activation of presynaptic cannabinoid type 1 (CB1) receptors. We further report that activation of CB1 receptors on GABAergic afferents to hilar mossy cells (by either endogenous or exogenous agonists) preferentially inhibits calcium-dependent exocytosis and that endocannabinoid-dependent retrograde signaling in this system is subject to tight spatial constraints.


2014 ◽  
Vol 307 (7) ◽  
pp. E580-E588 ◽  
Author(s):  
Edmund F. LaGamma ◽  
Necla Kirtok ◽  
Owen Chan ◽  
Bistra B. Nankova

Recurrent exposure to hypoglycemia can impair the normal counterregulatory hormonal responses that guard against hypoglycemia, leading to hypoglycemia unawareness. This pathological condition known as hypoglycemia-associated autonomic failure (HAAF) is the main adverse consequence that prevents individuals with type 1 diabetes mellitus from attaining the long-term health benefits of tight glycemic control. The underlying molecular mechanisms responsible for the progressive loss of the epinephrine response to subsequent bouts of hypoglycemia, a hallmark sign of HAAF, are largely unknown. Normally, hypoglycemia triggers both the release and biosynthesis of epinephrine through activation of nicotinic acetylcholine receptors (nAChR) on the adrenal glands. We hypothesize that excessive cholinergic stimulation may contribute to impaired counterregulation. Here, we tested whether administration of the nAChR partial agonist cytisine to reduce postganglionic synaptic activity can preserve the counterregulatory hormone responses in an animal model of HAAF. Compared with nicotine, cytisine has limited efficacy to activate nAChRs and stimulate epinephrine release and synthesis. We evaluated adrenal catecholamine production and secretion in nondiabetic rats subjected to two daily episodes of hypoglycemia for 3 days, followed by a hyperinsulinemic hypoglycemic clamp on day 4. Recurrent hypoglycemia decreased epinephrine responses, and this was associated with suppressed TH mRNA induction (a measure of adrenal catecholamine synthetic capacity). Treatment with cytisine improved glucagon responses as well as epinephrine release and production in recurrently hypoglycemic animals. These data suggest that pharmacological manipulation of ganglionic nAChRs may be promising as a translational adjunctive therapy to avoid HAAF in type 1 diabetes mellitus.


Author(s):  
Odell T. Minick ◽  
Hidejiro Yokoo

Mitochondrial alterations were studied in 25 liver biopsies from patients with alcoholic liver disease. Of special interest were the morphologic resemblance of certain fine structural variations in mitochondria and crystalloid inclusions. Four types of alterations within mitochondria were found that seemed to relate to cytoplasmic crystalloids.Type 1 alteration consisted of localized groups of cristae, usually oriented in the long direction of the organelle (Fig. 1A). In this plane they appeared serrated at the periphery with blind endings in the matrix. Other sections revealed a system of equally-spaced diagonal lines lengthwise in the mitochondrion with cristae protruding from both ends (Fig. 1B). Profiles of this inclusion were not unlike tangential cuts of a crystalloid structure frequently seen in enlarged mitochondria described below.


Author(s):  
G.J.C. Carpenter

In zirconium-hydrogen alloys, rapid cooling from an elevated temperature causes precipitation of the face-centred tetragonal (fct) phase, γZrH, in the form of needles, parallel to the close-packed <1120>zr directions (1). With low hydrogen concentrations, the hydride solvus is sufficiently low that zirconium atom diffusion cannot occur. For example, with 6 μg/g hydrogen, the solvus temperature is approximately 370 K (2), at which only the hydrogen diffuses readily. Shears are therefore necessary to produce the crystallographic transformation from hexagonal close-packed (hep) zirconium to fct hydride.The simplest mechanism for the transformation is the passage of Shockley partial dislocations having Burgers vectors (b) of the type 1/3<0110> on every second (0001)Zr plane. If the partial dislocations are in the form of loops with the same b, the crosssection of a hydride precipitate will be as shown in fig.1. A consequence of this type of transformation is that a cumulative shear, S, is produced that leads to a strain field in the surrounding zirconium matrix, as illustrated in fig.2a.


Author(s):  
J. C. Barry ◽  
H. Alexander

Dislocations in silicon produced by plastic deformation are generally dissociated into partials. 60° dislocations (Burgers vector type 1/2[101]) are dissociated into 30°(Burgers vector type 1/6[211]) and 90°(Burgers vector type 1/6[112]) dislocations. The 30° partials may be either of “glide” or “shuffle” type. Lattice images of the 30° dislocation have been obtained with a JEM 100B, and with a JEM 200Cx. In the aforementioned experiments a reasonable but imperfect match was obtained with calculated images for the “glide” model. In the present experiment direct structure images of 30° dislocation cores have been obtained with a JEOL 4000EX. It is possible to deduce the 30° dislocation core structure by direct inspection of the images. Dislocations were produced by compression of single crystal Si (sample preparation technique described in Alexander et al.).


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