Presynaptic Endings Research Articles

Cardioprotective effects of H3 receptor activation could be double-sided: insights from isoproterenol-induced cardiac injury.

Histamine H3 receptors (H3Rs) are known to modulate neurotransmitter release in the nervous system, but their role in cardiac injury remains unclear. The present study aimed to investigate the cardioprotective role of H3Rs in a mouse model of myocardial injury. Forty BALB/c male mice were divided into four groups: Control (SF), Isoproterenol (ISO), Imetit (IMT), and IMT + ISO. The IMT and IMT + ISO groups were pretreated orally with 10mg/kg imetit-dihydrobromide(imetit) for 7days. In the last 2days, the ISO and IMT + ISO groups received a subcutaneous injection of 85mg/kg isoproterenol to induce myocardial ischemia. Electrocardiogram (ECG) recordings were obtained, and heart tissues were analyzed histopathologically. The results demonstrated that the administration of imetit resulted in the prolongation of the PR interval in the IMT group. QRS and QT intervals were prolonged in the ISO group. The J-wave area in the ISO group was significantly larger than in the other groups. Histopathological analyses revealed the presence of small vacuoles, inflammatory cell infiltration, and collagen aggregates in cardiomyocytes in the ISO group. No significant cellular changes were observed in the IMT group, in contrast. The IMT + ISO group exhibited fewer ischemic findings than the ISO group. Immunohistochemical analyses revealed positive H3R immunoreactivity in all groups. Imetit pretreatment increased the immunoreactivity of H3Rs in both the IMT and IMT + ISO groups. The findings of this study suggest that H3Rs may be present on the postsynaptic side in cardiac myocytes, in addition to adrenergic presynaptic nerve endings. Furthermore, imetit has been found to significantly reduce the effects of myocardial ischemia by activating H3Rs. The better characterization of the postsynaptic role of H3Rs offers potential for the development of new therapeutic strategies.

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder

Abstract Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson’s disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43–87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1–3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson’s disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio < 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson’s disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson’s disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson’s disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

The Study of Neurons and Satellite Cells Under an Electron Microscope. Methodological Approaches

The main contribution of electron microscopy was the solution of problems concerning Nissl's substance, the Golgi apparatus, neurofibrils, myelin sheath and synapses. However, many problems remain unresolved due to the special nature of the neuron and the complexity of the structure of its processes. The use of an electron microscope led to the emergence of ideas about the structure and functions of the endoplasmic reticulum, protein, myelin sheath, Schwann cells, nodes of Ranvier, synapses, and the contents of presynaptic endings. This article presents the elements of the peripheral nervous system, new information about them and functions that can be further used in the study of the mechanisms of the occurrence of diseases and methods of treatment.

Impaired communication at the neuromotor axis during Degenerative Cervical Myelopathy.

Degenerative Cervical Myelopathy (DCM) is a progressive neurological condition characterized by structural alterations in the cervical spine, resulting in compression of the spinal cord. While clinical manifestations of DCM are well-documented, numerous unanswered questions persist at the molecular and cellular levels. In this study, we sought to investigate the neuromotor axis during DCM. We use a clinically relevant mouse model, where after 3 months of DCM induction, the sensorimotor tests revealed a significant reduction in both locomotor activity and muscle strength compared to the control group. Immunohistochemical analyses showed alterations in the gross anatomy of the cervical spinal cord segment after DCM. These changes were concomitant with the loss of motoneurons and a decrease in the number of excitatory synaptic inputs within the spinal cord. Additionally, the DCM group exhibited a reduction in the endplate surface, which correlated with diminished presynaptic axon endings in the supraspinous muscles. Furthermore, the biceps brachii (BB) muscle exhibited signs of atrophy and impaired regenerative capacity, which inversely correlated with the transversal area of remnants of muscle fibers. Additionally, metabolic assessments in BB muscle indicated an increased proportion of oxidative skeletal muscle fibers. In line with the link between neuromotor disorders and gut alterations, DCM mice displayed smaller mucin granules in the mucosa layer without damage to the epithelial barrier in the colon. Notably, a shift in the abundance of microbiota phylum profiles reveals an elevated Firmicutes-to-Bacteroidetes ratio-a consistent hallmark of dysbiosis that correlates with alterations in gut microbiota-derived metabolites. Additionally, treatment with short-chain fatty acids stimulated the differentiation of the motoneuron-like NSC34 cell line. These findings shed light on the multifaceted nature of DCM, resembling a synaptopathy that disrupts cellular communication within the neuromotor axis while concurrently exerting influence on other systems. Notably, the colon emerges as a focal point, experiencing substantial perturbations in both mucosal barrier integrity and the delicate balance of intestinal microbiota.

Age-Related Changes of the Synucleins Profile in the Mouse Retina

Alpha-synuclein (aSyn) plays a central role in Parkinson's disease (PD) and has been extensively studied in the brain. This protein is part of the synuclein family, which is also composed of beta-synuclein (bSyn) and gamma-synuclein (gSyn). In addition to its neurotoxic role, synucleins have important functions in the nervous system, modulating synaptic transmission. Synucleins are expressed in the retina, but they have been poorly characterized. However, there is evidence that they are important for visual function and that they can play a role in retinal degeneration. This study aimed to profile synucleins in the retina of naturally aged mice and to correlate their patterns with specific retinal cells. With aging, we observed a decrease in the thickness of specific retinal layers, accompanied by an increase in glial reactivity. Moreover, the aSyn levels decreased, whereas bSyn increased with aging. The colocalization of both proteins was decreased in the inner plexiform layer (IPL) of the aged retina. gSyn presented an age-related decrease at the inner nuclear layer but was not significantly changed in the ganglion cell layer. The synaptic marker synaptophysin was shown to be preferentially colocalized with aSyn in the IPL with aging. At the same time, aSyn was found to exist at the presynaptic endings of bipolar cells and was affected by aging. Overall, this study suggests that physiological aging can be responsible for changes in the retinal tissue, implicating functional alterations that could affect synuclein family function.

Neutralizing Antibodies to Botulinum Toxin Type A as a Secondary Treatment Failure: A Case Report from Mumbai, India

Botulinum toxin use in aesthetic medicine for treatment of facial rhytids is common and has become more and more popular in India in recent times. Botulinum toxin (BoNT) is produced by clostridium botulinum which is an anaerobic, spore forming, rod shaped bacteria. The botulinum toxin complex contains a 150 KD neurotoxin together with a complex additional protein. The neurotoxin is cleaved by the clostridial proteases into heavy and light chain. The heavy chain (100 KD) after cleavage binds to gangliosides and a protein receptor on the presynaptic nerve ending, whereas the light chain (50 KD) blocks the release of acetylcholine, leading to a dose dependent weakening of the target muscle.

Neuromuscular Junction Structural Charactaristics in Familial ALS Mice Model

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that can cause motor neuron degeneration in the spinal cord and motor cortex. Although most cases of ALS are sporadic, copper-zinc superoxide dismutase-1 (SOD1) mutations are responsible for 10%-20% of familial ALS.
 Objective: Studying neuromuscular junctions in various age groups to see how they vary in structure.
 Methods: From male hemizygous carriers (B6SJL-Tg (SOD1-G93A) 1Gur/J) and female B6SJL/F1 hybrids, female G93ASOD1 transgenic mice and age-matched wild-type (WT littermate partners, both were purchased from Jackson) laboratory. The animals were kept in an environment with controlled humidity and temperature, and 12:12h light was performed in a dark schedule, and sterile rodent food and sterile food were provided without specific pathogens.
 Results: WT and SOD1 are present in 40, 60, 90, 120 days of mice Inside the Tibialis anterior of G93ASOD1 mice (TA) and gastrocnemius (GN) construction. The neurofilament heavy polypeptide (tubulin, green) points to the presynaptic end. α-Bungarotoxins (BTX, white) mark the postsynaptic space, and synaptophysin (p38-1, red) is used for synaptic vesicles. In the following research we demonstrate that in 40 days of mice WT and SOD1 neither of them degraded while in 60 days of mice a slight denaturation occur in WT and SOD1 Further in 90 days of mice the degeneration is not serious about 60% to 70%. Furthermore, the deterioration in mice after 90 days is only 60-70 percent significant.
 Conclusion: NMJ inervation has appeared Disappearance, loss of motor axons, and huge structural damage to the NMJ at 60 and 90 days. Structural changes in presynaptic and postsynaptic structures and a gradual decrease in synaptic vesicles observe.

Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects.

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.

Synaptophysin is a selective marker for axons in human cutaneous end organ complexes

BackgroundSmall clear synaptic-like vesicles fill axon terminals of mechanoreceptors. Their functional significance is controversial and probably includes release of neurotransmitters from afferent axon terminals. Synaptophysin, a major protein of the synaptic vesicle membrane, is present in presynaptic endings of the central and peripheral nervous systems. It is also expressed in mechanosensory neurons which extend into skin forming sensory corpuscles. Nevertheless, synaptophysin occurrence in these structures has never been investigated. MethodsHere we used immunohistochemistry to detect synaptophysin in adult human dorsal root ganglia, cutaneous Meissner and Pacinian corpuscles and Merkel cell-neurite complexes from foetal to elderly period. Moreover, we analyzed whether synaptophysin co-localizes with the mechano-gated protein PIEZO2. ResultsSynaptophysin immunoreactivity was observed in primary sensory neurons (36 ± 6%) covering the entire soma size ranges. Axons of Meissner’s and Pacinian corpuscles were positive for synaptophysin from 36 and 12 weeks of estimated gestational age respectively, to 72 years old. Synaptophysin was also detected in Merkel cells (from 14 weeks of estimated gestational age to old age). Additionally in adult skin, synaptophysin and PIEZO2 co-localized in the axon of Meissner and Pacinian corpuscles, Merkel cells as well as in some axons of Merkel cell-neurite complexes. ConclusionPresent results demonstrate that a subpopulation of primary sensory neurons and their axon terminals forming cutaneous sensory corpuscles contain synaptophysin, a typical presynaptic vesicle protein. Although the functional relevance of these findings is unknown it might be related to neurotransmission mechanisms linked to mechanotransduction.

THE OPTIMIZATION OF THE RESULTS OF CHEMICAL MUSCLE DENERVATION THROUGH THE RECONSTITUTION OF BOTULINUM TOXIN TYPE A IN A STERILE INJECTABLE PHYSIOLOGICAL VEHICLE ENRICHED WITH ZINC

Botulinum toxin type A (TBA) is the most potent neurotoxin from the eight produced serotypes by the anaerobic gram-positive bacteria Clostridium Botulinum. To affect exclusively the nervous tissue, it is classified as neurotoxin. Its action promotes, within the presynaptic ending nerves, by blocking of the release of neurotransmitters, including acetylcholine. This nervous terminal incapacitation by the destruction of the SNAP25 protein binding loops in the SNARE complex is permanent. Labeled as Chemical Muscle Denervation, this non-invasive technique of significant relevance has aroused the interest of professionals and researchers from various areas and promoting a growing offer of new commercial options, protocol variations and clinical trials, in the aesthetic and therapeutic-functional segment. However, it has been observed lately a dissatisfaction of both professionals and patients, regarding the duration of the effects of the toxin, a reason that directly interferes with the interval between sessions, patient comfort and operating cost of treatments. When searching in the basic literature for concepts and justifications for the technical unpleasantness, in an integrated and interrelated way, it was observed that, as in any chemical phenomenon, chemical muscular denervation needs an ideal scenario. The pH level outside the proper standard at the TBA application site or the saline solution itself where the toxin was reconstituted, the sufficiency of zinc molecules for zinc-dependent reactions or even the choice and execution of protocols are simple examples of this need. The new literary focus brought as a diagnosis the existence of technical gaps, named in this study as “GAPs”, and which directly interfere in the success of procedures, when not identified and corrected. Two of these gaps, pH and zinc level will be presented and resolved in this article.

Efficacy of Magnesium Sulphate in Attenuation of Succinylcholine Induced FasciculationsA Randomised Clinical Study

Introduction: Magnesium Sulphate (MgSO4 ) pre-administration is effective in reducing Succinylcholine (Sch) induced fasciculations due to its effect at presynaptic end plate. Magnesium competes with calcium at the pre-synaptic end plate of neuromuscular junction and inhibits the release of acetylcholine (Ach) from the motor nerve terminal and to a lesser extent, decreases the sensitivity of the postjunctional membrane and reduces the excitability of the muscle fibre. Aim: To evaluate three doses of MgSO4 in reducing the incidence and severity of fasciculations and correlate with the serum magnesium levels. Materials and Methods: This prospective, randomised clinical trial was at Vijayanagar Institute of Medical Sciences (VIMS), Ballari, India. Ninety consenting adult patients aged 20-50 years scheduled for elective surgeries with endotracheal intubation under general anaesthesia were randomly allocated to three groups- Group 1, Group 2 and Group 3, to receive Injection (Inj.) MgSO4 20 mg/kg, 30 mg/kg and 40 mg/kg, respectively, before induction. Induction with Inj. propofol (2 mg/kg) was followed by administration of Inj. Sch (1.5 mg/kg). The main outcome parameters were the incidence of fasciculations and grading of the severity. Haemodynamic responses from the basal levels and after intubation, and adverse effects to the study drugs were noted. Chi-square test was used to find the significance of study parameters on categorical scale among the groups. Probability values at <0.05 were considered as significant. Results: The incidence of fasciculations was 90%, 53.4% and 43.4% in groups 1, 2 & 3, respectively. Greater number of patients had grade 3 fasciculations in group 1 (20%), compared to group 2 and group 3 (3.4% and nil) respectively. The fall in blood pressure after MgSO4 was comparable among the three groups. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) increased by 23.5% and 18.5%, 7.9% and 4.1% and 2.8% and 2.7% in groups 1, 2 and 3, respectively at one minute. The SBP and DBP at 3rd and 5th minute stayed at statistically significant greater levels in group 1 as compared to groups 2 and 3, but were similar in groups 2 and 3 overall. The Heart Rate (HR) changes followed similar trend in all 3 groups. Incidence of feeling of warmth was highest in group three as compared to other groups. Conclusion: MgSO4 at 40 mg/kg can be the optimal dose to suppress Sch-induced fasciculations, with better attenuation of intubation associated haemodynamic changes.

PECULIARITIES OF ELECTRON MICROSCOPIC HIPPOCAMPAL FORMATION DEVELOPMENT CHARACTERISTICS IN POSTERITY OF RATS AFTER PGE2 INJECTION FOR LABOR INDUCTION

The aim: To determine the peculiarities of electron microscopic hippocampal formation development characteristics in postetry of rats during two first weeks of postnatal life after intravaginal injection of prostaglandin E2 for labor induction. Materials and methods: The ultrastructural changes of hippocampal formation in posterity of white syngenic rats at the 1st, 7th and 14th days of postnatal life were examined. In this study we used electron-microscopic method. Brain tissue from experimental animals underwent standart stages necessary for electron microscopy and poured into pure Epon. Epon polymerization was carried out in two stages at 36 ° C (12 h) and 56 ° C (24 h). Ultrathin (50-60 nm) sections were obtained on a PowerTome RMC Boeckeler ultratome and then contrasted according to the E. Reynolds method. Ultrathin sections were studied in a PEM-100 electron microscope with an accelerating voltage 60 kV. Results: Based on the obtained data in the study of the hippocampal formation in postery of rats after induction of labor, analysis of the literature devoted to the electron microscopic study of the brain after ischemic injuries, it can be concluded that on the background of stimulation of labor by PgE2, changes corresponding to ischemic damage take place in the rat brain. Conclusions: In posterity of rats after receiving PgE2 for labour induction it was revealed microcirculatory changes; edema of the presynaptic endings, synaptic vesicles aggregation in the center of the presynaptic processes, swelling and destruction of mitochondria; oligodendroglia changes; ultrastructural changes in neurons like edema and vacuolization of mitochondria.

Mirogabalin as a Novel Gabapentinoid for the Treatment of Chronic Pain Conditions: An Analysis of Current Evidence.

Neuropathic pain is a challenge for physicians to treat and often requires a multimodal approach with both pharmacologic and lifestyle interventions. Mirogabalin, a potent, selective ligand of the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs), provides analgesia by inhibiting neurotransmitter release at the presynaptic end of the neuron. Mirogabalin offers more sustained analgesia than its gabapentinoid counterparts in addition to a wider safety margin for adverse events. Recent clinical trials of mirogabalin have demonstrated both efficacy and tolerability of the drug for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia, leading to its approval in Japan. While still not yet FDA approved, mirogabalin is still in its infancy and offers potential into the treatment of neuropathic pain and its associated comorbidities.

Choanoflagellates and the ancestry of neurosecretory vesicles.

Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore, important for animal cell–cell signalling. Despite considerable anatomical and functional diversity of neurons in animals, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many putative homologues of key neurosecretory vesicle proteins predate the origin of the first neurons, and some even the origin of the first animals. However, little is known about the molecular toolkit of these vesicles in non-bilaterian animals and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are present in unicellular organisms. Surprisingly, we find that the vesicular membrane-associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellate Salpingoeca rosetta. Our 3D vesicle reconstructions reveal that the choanoflagellates S. rosetta and Monosiga brevicollis exhibit a polarized and diverse vesicular landscape reminiscent of the polarized organization of chemical synapses that secrete the content of neurosecretory vesicles into the synaptic cleft. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses and neurons.This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.

Proteomic comparison of different synaptosome preparation procedures

Synaptosomes are frequently used research objects in neurobiology studies focusing on synaptic transmission as they mimic several aspects of the physiological synaptic functions. They contain the whole apparatus for neurotransmission, the presynaptic nerve ending with synaptic vesicles, synaptic mitochondria and often a segment of the postsynaptic membrane along with the postsynaptic density is attached to its outer surface. As being artificial functional organelles, synaptosomes are viable for several hours, retain their activity, membrane potential, and capable to store, release, and reuptake neurotransmitters. Synaptosomes are ideal subjects for proteomic analysis. The recently available separation and protein detection techniques can cope with the reduced complexity of the organelle and enable the simultaneous qualitative and quantitative analysis of thousands of proteins shaping the structural and functional characteristics of the synapse. Synaptosomes are formed during the homogenization of nervous tissue in the isoosmotic milieu and can be isolated from the homogenate by various approaches. Each enrichment method has its own benefits and drawbacks and there is not a single method that is optimal for all research purposes. For a proper proteomic experiment, it is desirable to preserve the native synaptic structure during the isolation procedure and keep the degree of contamination from other organelles or cell types as low as possible. In this article, we examined five synaptosome isolation methods from a proteomic point of view by the means of electron microscopy, Western blot, and liquid chromatography-mass spectrometry to compare their efficiency in the isolation of synaptosomes and depletion of contaminating subcellular structures. In our study, the different isolation procedures led to a largely overlapping pool of proteins with a fairly similar distribution of presynaptic, active zone, synaptic vesicle, and postsynaptic proteins; however, discrete differences were noticeable in individual postsynaptic proteins and in the number of identified transmembrane proteins. Much pronounced variance was observed in the degree of contamination with mitochondrial and glial structures. Therefore, we suggest that in selecting the appropriate isolation method for any neuroproteomics experiment carried out on synaptosomes, the degree and sort/source of contamination should be considered as a primary aspect.

Divergent Response to the SSRI Citalopram in Male and Female Three-Spine Sticklebacks (Gasterosteus aculeatus)

Selective serotonin reuptake inhibitors (SSRIs) are psychotropic pharmaceuticals used as antidepressants. SSRIs are commonly found in surface waters in populated areas across the globe. They exert their effect by blocking the serotonin re-uptake transporter in the presynaptic nerve ending. The present study examined whether behavioural effects to exposure to SSRI citalopram depend on personality and sex in the stickleback (Gasterosteus aculeatus). Three aspects of stickleback behaviour are examined: feeding behaviour, aggression, and boldness. We exposed sticklebacks to 350–380 ng/l citalopram for 3 weeks. Feeding and aggressive behaviour were recorded before and after exposure, whereas scototaxis behaviour was tested after exposure. The results show treatment effects in feeding and aggressive behaviour. Feeding is suppressed only in the male group (χ2 = 20.4, P < 0.001) but not in the females (χ2 = 0.91, P = 0.339). Aggressive behaviour was significantly affected by treatment (χ2 = 161.9, P < 0.001), sex (χ2 = 86.3, P < 0.001), and baseline value (χ2 = 58.8, P < 0.001). Aggressiveness was suppressed by citalopram treatment. In addition, the fish showed no change in aggression and feeding behaviour over time regardless of sex and treatment, which indicate personality traits. Only females are affected by treatment in the scototaxis test. The exposed females spent significantly (χ2 = 5.02, P = 0.050) less time in the white zone than the female controls.

S2043 Anxiolytic - A Gastric Fundus Relaxing Agent for Epigastric Pain Syndrome

INTRODUCTION: Functional dyspepsia (FD) is characterized by upper gastrointestinal symptoms such as early satiety, postprandial fullness, and epigastric pain or burning sensations. FD is commonly reported in women. According to the Rome III criteria, FD has two subtypes: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). In current clinical practice, the two subtypes often overlap in their presentation. Here, we present the case of a female patient who presented with symptoms of epigastric pain syndrome and achieved symptom relief with the anxiolytic gastric fundus relaxing agent buspirone. CASE DESCRIPTION/METHODS: A 71-year-old female with PMH of GERD, IBS, and anxiety that was well controlled with medications presented to the ED with complaints of non-radiating epigastric pain at a 7/10 intensity level intermittent since many months, and she reported no known aggravating or relieving factors. She denied any associated symptoms of nausea, vomiting, or diarrhea. In the past, she had been prescribed multiple medications such as antacids, PPI, and an anti-spasmodic agent for epigastric pain, and was also given antibiotics for possible SIBO. EGD revealed completely normal findings and no evidence of an ulcer or visible bleeding. The patient tested negative for H. pylori. After admission, she was started on a trial of 10 mg buspirone twice daily. She reported partial relief in the hospital and was discharged home. At the 1-month follow up at the GI clinic, the patient reported complete improvement in symptoms. DISCUSSION: EPS is characterized by symptoms such as an intermittent, non-generalized epigastric burning sensation, and a lack of relief with defecation or passage of flatus. Diagnosis of EPS remains exclusionary after all structural causes have been ruled out and according to the Rome III criteria, patients should have had symptoms for the past 3 months, and symptom onset should have occurred at least 6 months before the diagnosis. Reassurance and counseling have major roles. Other available agents such as antacids, PPIs, and prokinetics were reported in the treatment of EPS. Buspirone use for EPS has rarely been reported in the literature. Buspirone acts by activating 5 HT1A receptors on the presynaptic nerve endings of cholinergic neurons, thus inducing smooth muscle relaxation. Limited data are currently available on the efficacy of buspirone compared with other drugs used in the treatment of EPS. In the future, more research is needed to validate this use of buspirone.

Use of Dopamine Agonist in Tetanus Spasms - A Novel Approach to Revert the Respiratory Spasm - The Cause of Mortality

In tetanus patients Levodopa and Carbidopa combination (which is usually used to relieve the signs of extrapyramidal) causes respiratory muscles spasm relief thereby the need for sedatives is decreased and patient saved later on via central nervous system mechanism, by providing the inhibitory neurotransmitters at Anterior Horn cells. The tetanus toxin initially binds to peripheral nerve terminals then it retrogradely goes to CNS attaches with gangliosides at presynaptic inhibitory motor nerve endings, blocks glycine and gamma amino butyric acid (GABA) across the synaptic cleft.

The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses

HERC1 is a ubiquitin ligase protein, which, when mutated, induces several malformations and intellectual disability in humans. The animal model of HERC1 mutation is the mouse tambaleante characterized by: (1) overproduction of the protein; (2) cerebellar Purkinje cells death by autophagy; (3) dysregulation of autophagy in spinal cord motor neurons, and CA3 and neocortical pyramidal neurons; (4) impairment of associative learning, linked to altered spinogenesis and absence of LTP in the lateral amygdala; and, (5) motor impairment due to delayed action potential transmission, decrease synaptic transmission efficiency and altered myelination in the peripheral nervous system. To investigate the putative role of HERC1 in the presynaptic dynamics we have performed a series of experiments in cultured tambaleante hippocampal neurons by using transmission electron microscopy, FM1-43 destaining and immunocytochemistry. Our results show: (1) a decrease in the number of synaptic vesicles; (2) reduced active zones; (3) less clathrin immunoreactivity and less presynaptic endings over the hippocampal main dendritic trees; which contrast with (4) a greater number of endosomes and autophagosomes in the presynaptic endings of the tambaleante neurons relative to control ones. Altogether these results show an important role of HERC1 in the regulation of presynaptic membrane dynamics.

Взаимодействие между нервной и секреторной функциями в осуществлении интегративной деятельности нейросекреторной клетки Ретциуса пиявки

Based on the literature review and our own experimental data, it is shown how the two most important functions of the Retzius neuron (RN) of the medical leech — secretory and electrical — are related to each other. During low-frequency activation, RN behaves like a typical nerve cell, releasing serotonin from the presynaptic endings. During high-frequency stimulation, RN demonstrates properties a secretory cell, releasing serotonin by somatic exocytosis. The mechanism of autoinhibition (secretory function), revealed during highfrequency synaptic stimulation of RN, allows to prevent hyperactivation of its impulse activity (nervous function), which, in turn, through autoregulation inhibits hyperactivation of somatic exocytosis (secretory function). These data demonstrate that RN is a unique neurosecretory cell with polyfunctional activity.