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Cellular and Molecular Imaging of the Diabetic Pancreas
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Another distinctive feature of the pancreas is its heavy innervation. Parasympathetic nerves reach the pancreas through the vagus nerve and its branches, which interact with ganglia dispersed throughout the organ. In turn, these ganglia control the exocrine and endocrine pancreas through unmyelinated nerve fibers that secrete neurotransmitters such as acetylcholine and other polypeptides. Pancreatic islets are associated with higher levels of choline acetyltransferase and acetylcholinesterase than the remainder of the pancreas, and the majority of cholinergic activity appears focused on modulating beta-cell insulin secretion, glucose tolerance, and beta-cell proliferation. Consequently, the development of contrast agents that exploit these differential patterns of innervation and their relationship to insulin homeostasis represents a clear avenue to pursue. One example of such an agent is [18F]4-fluorobenzyltrozamicol (FBT), which is a radioactive tracer that binds to the vesicular acetylcholine transporter on presynaptic cholinergic neurons.12 Nuclear imaging with this tracer demonstrated a remarkably good accumulation in the pancreas of murine and primate models, higher than in any other organ. Furthermore, it was suggested that FBT activity may correlate closely with insulin-producing beta-cell innervation, mass, and function. This is particularly important, since it is believed that cholinergic innervation is reduced in type 1 diabetes.12
Neuroimaging
Published in John O'Brien, Ian McKeith, David Ames, Edmond Chiu, Dementia with Lewy Bodies and Parkinson's Disease Dementia, 2005
Both AD and DLB are associated with reduced levels of activity of the enzyme acetylcholinesterase (AChE) (Perry et al, 1980). AChE activity was investigated using PET among patients with PDD, AD, PD and controls (Bohnen et al, 2003). Patients with PDD were found to have the lowest level of activity, followed by those with PD, AD and controls, although AD patients showed a greater loss of activity in the medial temporal lobes. Using a marker of the vesicular acetylcholine transporter, significant differences between AD subjects and controls as well as between PD subjects with and without dementia have been found (Kuhl et al, 1996), although cases with DLB were not specifically examined. Cholinergic imaging has been relatively underutilized to date and may have a valuable role to play in detecting early cholinergic deficits at a presymptomatic stage.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
SYNAPTIC VESICLES are packaged with neurotransmitter molecules that are synthesized within neurons. The passage of NEUROTRANSMITTERS from the CYTOPLASM into vesicles is achieved using vesicular transporters, GLYCOPROTEIN molecules embedded in the vesicle membranes. ANTIBODIES to a number of these—the vesicular ACETYLCHOLINE transporter for example—now exist, enabling immunohistochemical localization studies (see IMMUNOHISTOCHEMISTRY) to plot the locations of terminals containing specific vesicular transporters (that is, terminals capable of releasing particular neurotransmitters).
Possible effects of different doses of 2.1 GHz electromagnetic radiation on learning, and hippocampal levels of cholinergic biomarkers in Wistar rats
Published in Electromagnetic Biology and Medicine, 2021
Çiğdem Gökçek-Saraç, Güven Akçay, Serdar Karakurt, Kayhan Ateş, Şükrü Özen, Narin Derin
For determination of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT) expressions, 15 µg of hippocampal samples were run on 7.5% polyacrylamide gels. The separated proteins were transferred onto the PVDF membrane using electroblotting with Mini Protean Tetra Cell equipment (Bio-Rad Laboratories, Richmond, CA, USA). Afterwards, the membranes were incubated at room temperature in a blocking solution made of 5% dried non-fat milk in TBS-T buffer (20 mM Tris-HCl, 0.5 M NaCl and 0.05% Tween 20, pH 7.6). Blots were then incubated for 2 h at room temperature with primary antibodies. Primary antibodies were applied at a dilution of 1:1000 (ChAT, ABCAM; AChE, ABCAM), and 1:250 (VAChT, NOVUS Biologicals). After being rinsed with TBS-T buffer, the membranes were incubated for 1 h at room temperature with the secondary alkaline phosphatase-conjugated antibody (ABCAM) used at a dilution of 1:3000 (ChAT, AChE) and 1:4000 (VAChT) in 5% dried non-fat milk in TBS-T buffer. A monoclonal antibody directed against β-actin was used as a control to normalize protein expression levels. Blots were rinsed with TBS-T buffer and incubated with an AP conjugate substrate kit (Bio-Rad) to visualize the specifically bound antibodies. The final images were photographed using a computer-based gel imaging instrument (VilberLourmat) with Infinity-Capt version 12.9 software. Immunoreactive protein bands were then quantified by densitometric scanning method using an Image J software package.
Does sympathetic nervous system modulate tumor progression? A narrative review of the literature
Published in Journal of Drug Assessment, 2020
Ioannis Stavropoulos, Angelos Sarantopoulos, Anastasios Liverezas
Zhang et al. [11] reported opposite findings by examining the distribution of sympathetic and parasympathetic nerve fibers in hepatocellular carcinoma (HCC) cells and their association with disease progression and severity. The investigators used specimens of cancerous tissue from 30 HCC patients. They matched 10 of these specimens with adjacent healthy tissue of the same patients and compared the distribution of autonomic fibers between non-cancerous and cancerous tissue. The density of sympathetic and parasympathetic nerve fibers was again assessed, by TH and vesicular acetylcholine transporter (VAChT) identification respectively, with immunohistochemical analysis. There was a higher expression of both TH and VaChT in HCC compared to non-cancer tissue. Furthermore, TH and VAChT expression were associated with vascular invasion, clinical stage and lower survival. TH intensity was also higher in the recurrence of the disease. The level of expression for various neurotransmitters receptors was examined in twelve types of hepatoma cells. Receptors expressed in most liver tumor cells were β2- and α1- adrenergic, α7 nicotinic AChr and M1 and M3 cholinergic receptors which possibly play a significant role in disease progression [11].
Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes
Published in Neurological Research, 2018
Yasmin S. Abulfadl, Nabila .N. El-Maraghy, Amany Ali. Eissa Ahmed, Shahira Nofal, Osama A. Badary
It has been recently reported that nitrosylation of vesicular acetylcholine transporter (VAChT), a neurotransmitter transporter which is responsible for loading ACh in neurons, may be associated with dysfunctional acetylcholinergic neurotransmission in AD [59]. In another study, nitrosylation of this transporter inhibits the vesicular uptake of acetylcholine in an animal model for AD [60,61]. According to these studies and in addition to our results, we suggest that TQ may prevent VAChT nitrosylation by scavenging NO and preventing it from attacking -SH of cysteine residues of VACht thereby making ACh available for secretion. TQ could therefore effectively enhance the induced cognitive impairment in our AD model. This suggestion is similar to that in a recent study [62] which stated that forebrain-specific deletion of VAChT has severe deficits in cognitive performance. Moreover, treatment with TQ (20 mg/kg, orally) succeeded to restore the brain content of BDNF. The protected level of this factor is likely to improve the synaptic efficacy and in turn improve cognition.