The Role of Mutations on HLA Genes in Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes. [1] The initial presentation can be similar to that of myasthenia gravis (MG), but the progressions of the 2 diseases have some important differences. LEMS disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca2+ channels involved with neurotransmitter release.

Different ideas on the pathogenesis and treatment of swine edema-disease

Although literature data associate the reason of swine edema-disease with certain serotypes of Escherichia coli bacteria, the authors assume that the primary cause of edema is more different. Susceptible agents and factors, mostly of feed compound are involved. During the digestion of some feed-origin protein opiate-like metabolites, exorphins arise, simultaneously arrest the release of acetylcholine. Consequences of acetylcholine shortage are spasm of sphincters (mostly pylorus), intestine-dilatation, contraction of bladder-sphincter, and urine retention. The endorphins and exorphins intensify the insulin release from the pancreas, hypoglycemia evolves, which is associated with loss of balance. According to the authors in edema-disease piglet dies because of hypoglycemia.

Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy

Botulinum neurotoxins (BoNTs) are potent inhibitors of synaptic vesicle fusion and transmitter release. The natural target of BoNTs is the peripheral neuromuscular junction (NMJ) where, by blocking the release of acetylcholine (ACh), they functionally denervate muscles and alter muscle tone. This leads them to be an excellent drug for the therapy of muscle hyperactivity disorders, such as dystonia, spasticity, and many other movement disorders. BoNTs are also effective in inhibiting both the release of ACh at sites other than NMJ and the release of neurotransmitters other than ACh. Furthermore, much evidence shows that BoNTs can act not only on the peripheral nervous system (PNS), but also on the central nervous system (CNS). Under this view, central changes may result either from sensory input from the PNS, from retrograde transport of BoNTs, or from direct injection of BoNTs into the CNS. The aim of this review is to give an update on available data, both from animal models or human studies, which suggest or confirm central alterations induced by peripheral or central BoNTs treatment. The data will be discussed with particular attention to the possible therapeutic applications to pathological conditions and degenerative diseases of the CNS.

Botulinum Neurotoxins (BoNTs) and Their Biological, Pharmacological, and Toxicological Issues: A Scoping Review

Botulinum toxins or neurotoxins (BoNTs) are the most potent neurotoxins known, and are currently extensively studied, not only for their potential lethality, but also for their possible therapeutic and cosmetic uses. Currently, seven types of antigenically distinct toxins are known and characterized, produced by a rod-shaped bacterium, Clostridium botulinum. Human poisoning by botulism (presenting with severe neuromuscular paralytic disease) is usually caused by toxins A, B, E, and F type. Poisoning from contaminated food preparations is the most common cause of noniatrogenic botulism. The spores are highly resistant to heat but are easily destroyed at 80 °C for thirty minutes. Type A and B toxins are resistant to digestion by the enzymes of the gastrointestinal system. After their entry, BoNTs irreversibly bind to cholinergic nerve endings and block the release of acetylcholine from the synapses. In contrast, in wound botulism, the neurotoxin is instead product by the growth of C.botulium in infected tissues. The contamination by BoNT inhalation does not occur by a natural route but it is certainly the most dangerous. It can be caused by the dispersion of the botulinum toxin in the atmosphere in the form of an aerosol and therefore can be deliberately used for bioterrorist purposes (e.g., during CBRN (chemical, biological, radiological, and nuclear) unconventional events). In addition, BoNTs are currently used to treat a variety of diseases or alleviate their symptoms, such as the onabotulinumtoxinA for migraine attacks and for cosmetic use. Indeed, this paper aims to report on updated knowledge of BoNTs, both their toxicological mechanisms and their pharmacological action.

Botulinum toxin in the treatment of neuralgia and neuropathic pain

Introduction: Botulinum toxin is one of the most powerful neurotoxins currently known, with high affinity to the cholinergic synapse, which sufficiently inhibits the release of acetylcholine. Its use has proved to be effective in the treatment of many diseases of the musculoskeletal system. Although most of the therapeutic effects of botulinum toxin are due to the temporary relaxation of skeletal muscles (caused by inhibition of acetylcholine release), research is ongoing into its effects on the nervous system. Purpose of the work: The aim of the study is to analyze the effectiveness of botulinum toxin in the treatment of neuralgia and neuropathic pain. Method: The relevant samples were accessed by means of an electronic search in the PubMed database. The analysis used reviews and meta-analyzes posted on the platform over the last 10 years. Conclusions: Botulinum toxin has great potential in the treatment of pain. It is multitasking due to its favorable safety profile and long-lasting relief from a single injection compared to other pain medications. The side effects caused by it were assessed to be mild to moderate and included a local skin reaction (swelling), injection site pain, muscle weakness, flu symptoms, nausea and vomiting. Keywords: botulinum toxin; neuropathic pain; pain treatment; neuralgia; BoNT / A

Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.

Atropine Reverts the Neurobehavioral Toxicity Elicited by Acute Exposure to Buprofezin in Sprague Dowley Rats

Buprofezin (BPFN) is a thiadiazine insecticide that inhibits chitin synthesis and the moulting in case of white flies, mealybugs and leaf hoppers. The exposed insects are unable to shed their cuticle and ultimately die as moulting ensue. Neurobehavioral toxic effects elicited by buprofezin remained unclear. Furthermore, the reversal of buprofezin induced neurobehavioral toxicity by atropine was not elaborated. Thus, we explored the neurobehavioral toxic consequences of acute buprofezin exposure in adult male rats and effective reversal of these changes by pretreatment with atropine as an antidote. Acute administration of commercial buprofezin (87.9mg/kg/day through oral gavage with corn oil as vehicle) induce a wide range of neurobehavioral toxicity including damage to pyramidal cells of hippocampal CA1, and CA3,region and behavioral impairments as demonstrated through, loss of motor coordination, locomotor activity, fear loss, hearing, sensorimotor, cognitive and spatial navigation impairment following the exposure .These neurobehavioral toxic effect of acute buprofezin exposure were significantly reversed by the 15 min pre-treatment of atropine antidote before the buprofezin administration. Pre-treated atropine (20mg/kg/day;i.p) attenuates the neurobehavioral toxicity induced by buprofezin in male rats. It was suggested that acute buprofezin exposure elevated the acetylcholine level, by inhibiting the synthesis and release of acetylcholine esterase (AChE) in synapse. But the complete mechanisms are remained to be elucidated

Physiology of cholinergic and adrenergic synapses. Role in pharmacology and practical significance

The transmission of signals between cholinergic neurons and from neurons to muscle cells (neuro-neuronal and neuromuscular transduction) occurs through synapses. They are formed by the membranes of two contacting cells, presynaptic and postsynaptic, which are separated by a narrow synaptic gap. The review article provides up-to-date information about the physiological processes in cholinergic and adrenergic synapses. The role of these synapses in pharmacology and their practical significance are presented. The transmission of excitation in cholinergic synapses occurs with the help of acetylcholine. The stages of synthesis, storage and release of acetylcholine are the same in all cholinergic neurons. The specific effects of acetylcholine mediated through cholinergic synapses depend mainly on the type of synaptic cholinergic receptors. In the system of efferent innervation, adrenergic synapses are formed by the endings of postganglionic sympathetic (adrenergic) fibers and cells of effector organs.