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Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
2016: Skeletal Muscle
Marco Kramer, Diogo Ribeiro, Marie Arsenian-Henriksson, Thomas Deller, Hermann Rohrer
: Neuroblastoma (NB) is a childhood tumor that arises from the sympathoadrenal lineage. MYCN amplification is the most reliable marker for poor prognosis and MYCN overexpression in embryonic mouse sympathetic ganglia results in NB-like tumors. MYCN cooperates with mutational activation of anaplastic lymphoma kinase (ALK), which promotes progression to NB, but the role of MYCN and ALK in tumorigenesis is still poorly understood. Here, we use chick sympathetic neuroblasts to examine the normal function of MYCN and MYC in the control of neuroblast proliferation, as well as effects of overexpression of MYCN, MYC, and activated ALK, alone and in combination...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Pedro A Pereira, Tiago Millner, Manuel Vilela, Sérgio Sousa, Armando Cardoso, M Dulce Madeira
The medial prefrontal cortex (mPFC) has been identified as a critical center for working and long-term memory. In this study, we have examined the expression of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in mPFC interneurons and the density of the mPFC cholinergic and dopaminergic innervation in cognitively-impaired aged Wistar rats. We also tested the possibility that the potential age-related changes might rely on insufficient neurotrophic support. The total number of NPY- and VIP-immunoreactive neurons and the density of vesicular acetylcholine transporter (VAChT)- and tyrosine hydroxylase (TH)-immunoreactive varicosities were estimated using stereological methods...
September 21, 2016: Experimental Gerontology
Dawid Walas, Eva Von Roloff, Julian Paton
OBJECTIVE: Our hypothesis is that hypoperfusion of the brainstem is due to elevated vertebrobasilar artery resistance, triggers hypertension. We asked: is there a functional relationship between the sympathetic innervation to the vertebrobasilar system and its remodelling in the SHR? DESIGN AND METHOD: SHRs (11-12 weeks old) received either sham surgery or bilateral SCGx. Animals recovered for 14 days, were then perfused-fixed with 4% PFA and the vertebrobasilar arteries examined using both immunohistofluorecent staining of sympathetic (anti-DβH) and parasympathetic (anti-VAChT) fibres, and by cross sectional examination of vertebral and basilar arteries...
September 2016: Journal of Hypertension
Vania F Prado, Helena Janickova, Mohammed A Al-Onaizi, Marco A M Prado
Cognitive flexibility, the ability to adjust behavior in response to new and unexpected conditions in the environment, is essential for adaptation to new challenges and survival. The cholinergic system is an important modulator of this complex behavior however, the exact cholinergic circuits involved in this modulation and the precise influence of acetylcholine (ACh) in the process is still not fully understood. Here we review the role of different cholinergic circuits in cognitive flexibility. Strong evidence indicates that cholinergic interneurons (CINs) from the dorsomedial striatum are essential for facilitating the establishment of a new selected strategy; an effect that seems to depend mainly on activation of muscarinic receptors...
September 15, 2016: Neuroscience
Hidemi Misawa, Daijiro Inomata, Miseri Kikuchi, Sae Maruyama, Yasuhiro Moriwaki, Takashi Okuda, Nobuyuki Nukina, Tomoyuki Yamanaka
VAChT-Cre.Fast and VAChT-Cre.Slow mice selectively express Cre recombinase in approximately one half of post-natal somatic motor neurons. The mouse lines have been used in various studies with selective genetic modifications in adult motor neurons. In the present study, we crossed VAChT-Cre lines with a reporter line, CAG-Syp/tdTomato, in which synaptophysin-tdTomato fusion proteins are efficiently sorted to axon terminals, making it possible to label both cell bodies and axon terminals of motor neurons. In the mice, Syp/tdTomato fluorescence preferentially co-localized with osteopontin, a recently discovered motor neuron marker for slow-twitch fatigue-resistant (S) and fast-twitch fatigue-resistant (FR) types...
September 6, 2016: Genesis: the Journal of Genetics and Development
Gina L O'Grady, Corien Verschuuren, Michaela Yuen, Richard Webster, Manoj Menezes, Johanna M Fock, Natalie Pride, Heather A Best, Tatiana Benavides Damm, Christian Turner, Monkol Lek, Andrew G Engel, Kathryn N North, Nigel F Clarke, Daniel G MacArthur, Erik-Jan Kamsteeg, Sandra T Cooper
OBJECTIVE: To describe the clinical and genetic characteristics of presynaptic congenital myasthenic syndrome secondary to biallelic variants in SLC18A3. METHODS: Individuals from 2 families were identified with biallelic variants in SLC18A3, the gene encoding the vesicular acetylcholine transporter (VAChT), through whole-exome sequencing. RESULTS: The patients demonstrated features seen in presynaptic congenital myasthenic syndrome, including ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water for patient 1...
October 4, 2016: Neurology
Li Chen, Dian-Hua Liu, Xin Zhang, En-Hui Zhang, Chong Liu, Ding-Feng Su, Guo-Jun Cai
OBJECTIVE: Inflammation and oxidative stress play a key role in the initiation, propagation, and development of atherosclerosis. Arterial baroreflex (ABR) dysfunction induced by sinoaortic denervation (SAD) promoted the development of atherosclerosis in ApoE(-/-) mice. The present work was designed to examine whether ABR deficiency affected inflammation and oxidative stress via α7 nicotinic acetylcholine receptor (α7nAChR) leading to the aggravation of atherosclerosis in mice. METHODS AND RESULTS: ApoE(-/-) mice were fed with a high-cholesterol diet for 6weeks and half of the mice received sinoaortic denervation that destroyed ABR...
August 24, 2016: Vascular Pharmacology
Olga Gajewska-Woźniak, Kamil Grycz, Julita Czarkowska-Bauch, Małgorzata Skup
The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG)...
2016: PloS One
Reinaldo Correia Silva, Fernanda Fernandes Terra, Yuri Felipe Guise, Marco Antônio Máximo Prado, Vânia Ferreira Prado, Meire Ioshie Hiyane, Denise Maria Avancini Costa Malheiros, Carla Maximo Prado, Niels Olsen Saraiva Camara, Tarcio Teodoro Braga
Chronic kidney disease (CKD) is associated with several other long-lasting conditions such as diabetes and cardiovascular diseases and it is a significant contributor to mortality worldwide. Obstructive kidney disease is one of the leading causes of CKD in children and may result from a wide variety of pathologic processes. Recent studies have shown that α7 nicotinic acetylcholine receptor (α7 nAChR) activation in the cholinergic anti-inflammatory pathway reduces production of inflammatory mediators and consequently prevents tissue injury and death...
September 2016: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Shahdat Hossain, Sujan Bhowmick, Sabrin Jahan, Liza Rozario, Marzan Sarkar, Saiful Islam, Mafroz Ahmed Basunia, Azizur Rahman, Bazlul Karim Choudhury, Hussain Shahjalal
The presence of lead (Pb) in fetal brain may affect brain development-related proteins. We studied whether gestational/lactational Pb-exposure affects oxidative stress, proinflammatory response, apoptosis and levels of brain development/cognition-related proteins, including presynaptic synaptosome-associated protein-25 (SNAP-25), postsynaptic density protein-95 (PSD-95), brain-derived neurotropic factor (BDNF), tyrosine receptor-kinase protein B (TrkB) and vesicular acetylcholine transporter (VAChT) in the offspring...
September 2016: Neurotoxicology
Ahmed A Rahman, Ainsley M Robinson, Simon J H Brookes, Rajaraman Eri, Kulmira Nurgali
Rectal prolapse is associated with diminished anal sensitivity and rectal motor activity. Both sensory and motor functions are controlled by the extrinsic and intrinsic (enteric nervous system) innervation of the gastrointestinal tract. Studies of changes in intestinal innervation in humans and in animal models with rectal prolapse are extremely scarce. The Winnie mouse model of spontaneous chronic colitis closely represents human inflammatory bowel disease and is prone to develop rectal prolapse. We have investigated changes in the myenteric and inhibitory motor neurons and evaluated changes in the density of sensory afferent, sympathetic, and parasympathetic fibers in the rectal colon of Winnie mice with and without rectal prolapse...
August 1, 2016: Cell and Tissue Research
Joachim Mazère, Frederic Lamare, Philippe Fernandez, Michèle Allard, Willy Mayo
: Cholinergic alterations in Dementia with Lewy bodies (DLB) are widely documented in post mortem studies whereas in vivo studies are sparse, particularly at subcortical level. We used (123)I-iodobenzovesamicol, a single Photon Emission Computed Tomography (SPECT) radiotracer of the Vesicular Acetylcholine Transporter (VAChT), to evaluate in vivo in DLB the integrity of the three main cholinergic pathways: the Ch1 (septo-hippocampal), the Ch4 (innominato-cortical) and the Ch5 (ponto-thalamic) cholinergic pathways, as well as the striatal cholinergic interneurons...
July 28, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Benjamin N Breyer, Thomas M Fandel, Amjad Alwaal, E Charles Osterberg, Alan W Shindel, Guiting Lin, Emil A Tanagho, Tom F Lue
OBJECTIVE: To compare the effect of complete transection (tSCI) and contusion injury (cSCI) on bladder function and bladder wall structure in rats. MATERIALS AND METHODS: 30 female Sprague-Dawley rats were randomly divided into three equal groups: uninjured controls, cSCI, and tSCI. The cSCI group underwent spinal cord contusion, while the tSCI group underwent complete spinal cord transection. 24-hour metabolic cage measurement and conscious cystometry were performed at 6 weeks post-injury...
July 19, 2016: BJU International
Jittima Gotts, Lucy Atkinson, Yuchio Yanagawa, Jim Deuchars, Susan A Deuchars
Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry...
September 1, 2016: Brain Research
A Dudek, W Sienkiewicz, A Chrószcz, M Janeczek, J Kaleczyc
Immunohistochemical properties of nerve fibres supplying the joint capsule were previously described in many mammalian species, but the localization of sensory neurons supplying this structure was studied only in laboratory animals, the rat and rabbit. However, there is no comprehensive data on the chemical coding of sensory neurons projecting to the hip joint capsule (HJC). The aim of this study was to establish immunohistochemical properties of sensory neurons supplying HJC in the sheep. The study was carried out on 10 sheep, weighing about 30-40 kg...
June 28, 2016: Anatomia, Histologia, Embryologia
Benjamin Kolisnyk, Mohammed Al-Onaizi, Lilach Soreq, Shahar Barbash, Uriya Bekenstein, Nejc Haberman, Geula Hanin, Maxine T Kish, Jussemara Souza da Silva, Margaret Fahnestock, Jernej Ule, Hermona Soreq, Vania F Prado, Marco A M Prado
The relationship between long-term cholinergic dysfunction and risk of developing dementia is poorly understood. Here we used mice with deletion of the vesicular acetylcholine transporter (VAChT) in the forebrain to model cholinergic abnormalities observed in dementia. Whole-genome RNA sequencing of hippocampal samples revealed that cholinergic failure causes changes in RNA metabolism. Remarkably, key transcripts related to Alzheimer's disease are affected. BACE1, for instance, shows abnormal splicing caused by decreased expression of the splicing regulator hnRNPA2/B1...
June 16, 2016: Cerebral Cortex
Bo-Shi Fan, En-Hui Zhang, Ming-He Cheng, Zhao-Tang Wu, Bing Han, Jian-Guang Yu
AIMS: Cholinergic antiinflammatory (CAI) pathway functions importantly in inflammation via α7 nicotinic acetylcholine receptors (α7nAChR). The present work tested circadian rhythm in peripheral CAI activity and validities of CAI activity and glucocorticoids in chronotherapy for lipopolysaccharide (LPS)-induced shock. METHODS: Vesicular acetylcholine transporter (VAChT) expressed in liver and kidney was examined every 3 h in C57BL/6 mice. Proinflammatory cytokines in serum and survival time in shock were monitored after LPS injection every 3 h...
September 2016: CNS Neuroscience & Therapeutics
Daniel Palmer, Samantha Creighton, Vania F Prado, Marco A M Prado, Elena Choleris, Boyer D Winters
Substantial evidence implicates Acetylcholine (ACh) in the acquisition of object memories. While most research has focused on the role of the cholinergic basal forebrain and its cortical targets, there are additional cholinergic networks that may contribute to object recognition. The striatum contains an independent cholinergic network comprised of interneurons. In the current study, we investigated the role of this cholinergic signalling in object recognition using mice deficient for Vesicular Acetylcholine Transporter (VAChT) within interneurons of the striatum...
September 15, 2016: Behavioural Brain Research
Lingfu Zhang, Limei Guo, Ming Tao, Wei Fu, Dianrong Xiu
OBJECTIVE: To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma (PDAC). METHODS: Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter (VAChT), as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information...
April 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
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