Nucleus Area Research Articles

Divergent projections from locus coeruleus to the corticobasal ganglia system and ventral tegmental area of the adult male zebra finch.

The locus coeruleus (LC) is a small noradrenergic brainstem nucleus that plays a central role in regulating arousal, attention, and performance. In the mammalian brain, individual LC neurons make divergent axonal projections to different brain regions, which are distinguished in part by which noradrenaline (NA) receptor subtypes they express. Here, we sought to determine whether similar organizational features characterize LC projections to corticobasal ganglia (CBG) circuitry in the zebra finch song system, with a focus on the basal ganglia nucleus Area X, the thalamic nucleus DLM, as well as the cortical nuclei HVC, LMAN, and RA. Single and dual retrograde tracer injections reveal that single LC-NA neurons make divergent projections to LMAN and Area X, as well as to the dopaminergic VTA/SNc complex that innervates this CBG circuit. Moreover, in situ hybridization revealed that differential expression of mRNA encoding α2A and α2C adrenoreceptors distinguishes LC-recipient CBG song nuclei. Therefore, LC-NA signaling in the zebra finch CBG circuit employs a similar strategy as in mammals, which could allow a relatively small number of LC neurons to exert widespread yet distinct effects across multiple brain regions.

Comparison of Ultra-Magnifying Endocytoscopic and Hematoxylin-Eosin-Stained Images of Lung Specimens

Endocytoscopy enables real-time observation of lesions at ultra-magnification. In the gastrointestinal and respiratory fields, endocytoscopic images are similar to hematoxylin-eosin-stained images. This study aimed to compare the nuclear features of pulmonary lesions in endocytoscopic and hematoxylin-eosin-stained images. We performed an endocytoscopy to observe resected specimens of normal lung tissue and lesions. Nuclear features were extracted using ImageJ. We analyzed five nuclear features: nuclear number per area, mean nucleus area, median circularity, coefficient of variation of roundness, and median Voronoi area. We conducted dimensionality reduction analyses for these features, followed by assessments of the inter-observer agreement among two pathologists and two pulmonologists to evaluate endocytoscopic videos. We analyzed the nuclear features of hematoxylin-eosin-stained and endocytoscopic images from 40 and 33 cases, respectively. Endocytoscopic and hematoxylin-eosin-stained images displayed a similar tendency for each feature, despite there being no correlation. Conversely, the dimensionality reduction analyses demonstrated similar distributions of normal lung and malignant clusters in both images, thus differentiating between the clusters. The diagnostic accuracy of the pathologists was 58.3% and 52.8% (κ-value 0.38, fair), and that of the pulmonologists was 50% and 47.2% (κ-value 0.33, fair). The five nuclear features of pulmonary lesions were similar in the endocytoscopic and hematoxylin-eosin-stained images.

Morphological and immunological markers of repeated heart remodeling after surgical reconstruction of the left ventricle in ischemic cardiomyopathy.

Effective treatment of patients with ischemic cardiomyopathy (ICM) is one of the most challenging issues in modern cardiac surgery. The aim of this study was to assess the state of cardiomyocytes and myocardial extracellular matrix, as well as to identify informative markers of an unfavorable prognosis for surgical treatment of ICM. We retrospectively reviewed patients who underwent surgical treatment of ICM between 2011 and 2018 at a single center. Patients were divided into groups depending on the presence of repeated left ventricle (LV) remodeling in one-year follow-up after surgical reconstruction of the LV in ICM patients. A total of 45 patients with ICM were reviewed. The mean age of the patients was 57.9 ± 7.8 years. According to the results of the study, the area of cardiomyocyte nuclei differed statistically significantly among the regions with varying degrees of impaired local contractility (p = 0.042). According to the results of the pairwise comparison in dyskinetic areas of the myocardium, the area of cardiomyocyte nuclei was higher than in normokinetic areas (p = 0.042). A moderate positive correlation was found between the LV ejection fraction measured in one-year follow-up period after surgery and the number of CD163-positive cells (p = 0.012). In the myocardium of patients with LV reverse remodeling in the long-term postoperative period, perivascular fibrosis occurs more frequently than in patients with progressive LV remodeling. The number of M2-anti-inflammatory macrophages prevails in the myocardium of the patients with reverse remodeling compared with patients with progressive remodeling.

A parametric blueprint for optimum cochlear outer hair cell design.

The present work examines the hypothesis that cochlear outer hair cell (OHC) properties vary in precise proportions along the tonotopic map to optimize electromechanical power conversion. We tested this hypothesis using a very simple model of a single isolated OHC driving a mechanical load. Results identify three non-dimensional ratios that are predicted to optimize power conversion: the ratio of the resistive-capacitive (RC) corner to the characteristic frequency (CF), the ratio of nonlinear to linear capacitance and the ratio of OHC stiffness to cochlear load stiffness. Optimum efficiency requires all three ratios to be universal constants, independent of CF and species. The same ratios are cardinal control parameters that maximize power output by positioning the OHC operating point on the edge of a dynamic instability. Results support the hypothesis that OHC properties evolved to optimize electro-mechanical power conversion. Identification of the RC corner frequency as a control parameter reveals a powerful mechanism used by medial olivocochlear efferent system to control OHC power output. Results indicate the upper-frequency limit of OHC power output is not constrained by the speed of the motor itself but instead is probably limited by the size of the nucleus and membrane surface area available for ion-channel expression.

Excessive daytime sleepiness in a model of Parkinson’s disease improved by low-frequency stimulation of the pedunculopontine nucleus

Patients with Parkinson’s disease often complain of excessive daytime sleepiness which negatively impacts their quality of life. The pedunculopontine nucleus, proposed as a target for deep brain stimulation to improve freezing of gait in Parkinson’s disease, is also known to play a key role in the arousal system. Thus, the putative control of excessive daytime sleepiness by pedunculopontine nucleus area stimulation merits exploration for treating Parkinson’s disease patients. To this end, two adult nonhuman primates (macaca fascicularis) received a deep brain stimulation electrode implanted into the pedunculopontine nucleus area along with a polysomnographic equipment. Stimulation at low frequencies and high frequencies was studied, in healthy and then MPTP-treated nonhuman primates. Here, we observed that MPTP-treated nonhuman primates suffered from excessive daytime sleepiness and that low-frequency stimulation of the pedunculopontine nucleus area was effective in reducing daytime sleepiness. Indeed, low-frequency stimulation of the pedunculopontine nucleus area induced a significant increase in sleep onset latency, longer continuous periods of wakefulness and thus, a partially restored daytime wake architecture. These findings may contribute to the development of new therapeutic strategies in patients suffering from excessive daytime sleepiness.

Interactions of alcohol and combination antiretroviral (cART) drug in diabetic male Sprague Dawley rats: Hippocampal perturbations and toxicosis.

Hippocampal pathology in diabetes is constantly investigated but the resultant health impact of the concomitant presence of alcohol and combined antiretroviral therapy (cART) in diabetes requires further studies to delineate toxicities inimical to hippocampal normal function. Forty-eight male Sprague Dawley rats were divided into eight groups (n=6): negative control (NC), alcohol (AL), cART (AV), alcohol-cART (AA), diabetic control (DB), diabetes-alcohol (DAL), diabetes-cART (DAV), and diabetes-alcohol-cART (DAA) exposure groups. Following diabetes induction and sub-chronic (90 days) treatment exposure, hippocampal homogenates were profiled for pro-inflammatory cytokines and oxidative stress (MDA and GPx) using immunoassay, while apoptotic genes (BAX, Bcl2, and Caspase-3), insulin receptor genes (INSR and IRS-1), and blood-brain barrier (BBB) junctional proteins (claudin-5, and occludin) gene expression were assessed using qPCR. Histomorphology of hippocampal neuronal number, nuclei area, and volume of dentate gyrus and neurogenesis were accessed using Giemsa stain, Ki67, and DCX histochemistry respectively. A central hippocampal effect that underpins all treatments is the reduction of DG neuronal number and antioxidant (GPx), highlighting the venerability of the hippocampal dentate gyrus neurons to diabetes, alcohol, cART, and their combinatorial interactions. Additionally, elevated BAX, Bcl2, and IRS1 mRNA levels in the DAL group, and their downregulation in AA, suggests IRS-1-regulated apoptosis due to differential modulating effects of alcohol treatment in diabetes (DAL) in contrast to alcohol with cART (AA). Although the interaction in AA therapy ameliorated the independent alcohol and cART effects on MDA levels, pro-inflammatory cytokines, and DCX, the interaction in AA exacerbated a deficiency in the expression of INSR, IRS-1 (insulin sensitivity), and BBB mRNA which are implicated in the pathogenies of diabetes. Furthermore, the diabetic comorbidity groups (DAV, DAL, and DAA) all share a central effect of elevated hippocampal oxidative stress, BAX, and Caspase-3 mRNA expression with the reduced number of hippocampal neurons, dentate gyrus volume, and neurogenesis, highlighting neurodegenerative and cognitive deficiency implication of these comorbidity treatments. Considering these findings, assessment of hippocampal well-being in patients with these comorbidities/treatment combinations is invaluable and caution is advised particularly in alcohol use with cART prophylaxis in diabetes.

СРАВНИТЕЛЬНЫЙ ЛЕЙКОЦИТАРНЫЙ ПРОФИЛЬ И РАЗМЕРНЫЕ ХАРАКТЕРИСТИКИ КЛЕТОК КРОВИ СУХОПУТНЫХ ЧЕРЕПАХ ИЗ САМАРСКОГО ЗООПАРКА

A comparative analysis of leukograms and morphometric features of blood cells of three species of tortoises from the Samara Zoo was carried out: Testudo horsfi eldii Gray, 1844; Geochelone elegans (Schoepff, 1795); Chelonoidis carbonarius (Spix, 1824). Interspecies statistically signifi cant differences in the total content of agranulocytes and granulocytes were revealed. The leukocyte profi le indicated a pronounced innate immune response in tortoises and a more active cell-mediated adaptive response in C. carbonarius. According to the totality of integral indicators of the leukocyte profi le, the most stable and balanced immune response was noted in T. horsfi eldii. The variability of karyocytometric parameters of turtle blood cells was revealed. The share of variability in the area of cell nuclei, depending on the area of the cell itself, was the highest for different cells in different species: T. horsfi eldii (basophils), G. elegans (platelets), C. carbonarius (eosinophils). The area of blood cells (with the exception of eosinophils) and the nuclearcytoplasmic ratios of cells of the same type in different turtle species varied. A higher metabolic activity of blood cells of T. horsfi eldii was established in comparison with G. elegans and C. carbonarius.

Morphology of the testes of animals during estrogen injection in the prenatal period

The aim of the study was to investigate the morphological changes in the testes of the offspring of white non-pedigreed laboratory mice when the synthetic oestrogen analogue synestrol was prenatally injected to the mother. After fertilization, the females were divided into 2 groups which received a single intramuscular injection of the synthetic oestrogen analogue synestrol on day E 11.5 of gestation at the same time of the day. The intact group was not exposed to any treatment. The experimental group was exposed to synestrol, a synthetic oestrogen analogue, as a 2% oil solution at a dose of 40 µg/kg (C-40). The results of morphometric analysis of testes of descendants of white outbred laboratory mice after prenatal single injection of synthetic oestrogen analogue synestrol in a dose of 40 µg/kg showed morphological changes in the organ parenchyma, manifested as decrease in mean number of Sertoli cells (C-40) 17.4±1.1 compared to intact group 20.8±1.9; decrease in mean number of spermatogonia (C-40) 24.4±1.1 compared to intact group, decrease in mean number of spermatozoa (C-40) 178.0±4.2 compared to intact group 196.6±5.3. There was observed a change in the endocrine apparatus of testes, expressed as a decrease in the mean area of Leydig cell nuclei in the intact group of 6,72±1,78. Prenatal effects of synestrol revealed in an experimental model, allow us to use it to search for means of postnatal developmental testicular dysfunction correction as well as to develop optimal doses of oestrogenic preparations during pregnancy.

Hippocampal, Whole Midbrain, Red Nucleus, and Ventral Tegmental Area Volumes Are Increased by Selective Breeding for High Voluntary Wheel-Running Behavior.

Uncovering relationships between neuroanatomy, behavior, and evolution are important for understanding the factors that control brain function. Voluntary exercise is one key behavior that both affects, and may be affected by, neuroanatomical variation. Moreover, recent studies suggest an important role for physical activity in brain evolution. We used a unique and ongoing artificial selection model in which mice are bred for high voluntary wheel-running behavior, yielding four replicate lines of high runner (HR) mice that run ∼3-fold more revolutions per day than four replicate nonselected control (C) lines. Previous studies reported that, with body mass as a covariate, HR mice had heavier whole brains, non-cerebellar brains, and larger midbrains than C mice. We sampled mice from generation 66 and used high-resolution microscopy to test the hypothesis that HR mice have greater volumes and/or cell densities in nine key regions from either the midbrain or limbic system. In addition, half of the mice were given 10 weeks of wheel access from weaning, and we predicted that chronic exercise would increase the volumes of the examined brain regions via phenotypic plasticity. We replicated findings that both selective breeding and wheel access increased total brain mass, with no significant interaction between the two factors. In HR compared to C mice, adjusting for body mass, both the red nucleus (RN) of the midbrain and the hippocampus (HPC) were significantly larger, and the whole midbrain tended to be larger, with no effect of wheel access nor any interactions. Linetype and wheel access had an interactive effect on the volume of the periaqueductal gray (PAG), such that wheel access increased PAG volume in C mice but decreased volume in HR mice. Neither linetype nor wheel access affected volumes of the substantia nigra, ventral tegmental area, nucleus accumbens, ventral pallidum (VP), or basolateral amygdala. We found no main effect of either linetype or wheel access on neuronal densities (numbers of cells per unit area) for any of the regions examined. Taken together, our results suggest that the increased exercise phenotype of HR mice is related to increased RN and hippocampal volumes, but that chronic exercise alone does not produce such phenotypes.

Brain dysfunction in gait disorders of Caribbean atypical Parkinsonism and progressive supranuclear palsy patients: A comparative study

IntroductionGait disorders and falls occur early in progressive supranuclear palsy (PSP-RS) and Caribbean atypical parkinsonism (Caribbean AP). However, the link between these signs and brain lesions has never been explored in these patient populations. Here, we investigate and compare the imaging factors that relate to gait and balance disorders in Caribbean AP and PSP-RS patients. MethodsWe assessed gait and balance using clinical scales and gait recordings in 16 Caribbean AP and 15 PSP-RS patients and 17 age-matched controls. We measured the grey and white matter brain volumes on 3 T brain MRI images. We performed a principal component analysis (PCA) including all the data to determine differences and similarities between groups, and explore the relationship between gait disorders and brain volumes. ResultsBoth Caribbean AP patients and PSP-RS have marked gait and balance disorders with similar severity. In both groups, gait and balance disorders were found to be most strongly related to structural changes in the lateral cerebellum, caudate nucleus, and fronto-parietal areas. In Caribbean AP patients, gait disorders were also related to additional changes in the cortex, including frontal, insular, temporal and cuneus lobes, whereas in PSP-RS patients, additional white matter changes involved the mesencephalon and parahippocampal gyrus. ConclusionGait and balance disorders in Caribbean AP patients are mainly related to dysfunction of cortical brain areas involved in visuo-sensorimotor processing and self-awareness, whereas these signs mainly result from premotor-brainstem-cerebellar network dysfunction in PSP-RS patients, brain areas involved in initiation and maintenance of locomotor pattern and postural adaptation.

Clinical and neuroimaging comparisons of acute cerebrovascular accident against the background of ­COVID‑19

Objective — to compare clinical data with the results of neuroimaging methods of brain research in patients with acute cerebrovascular accident against the background of ­COVID‑19.
 Methods and subjects. The medical histories of 72 patients (47 (65.3 %) men and 25 (34.7 %) women) with the diagnosis of acute cerebrovascular accident and coronavirus infection were retrospectively analyzed. In the reception department, all patients with suspected stroke were examined by a neurologist, all patients were examined with a computed tomography scan of the brain, and a smear was taken for polymerase chain reaction (PCR) for ­SARS‑CoV‑2. If necessary, the patient was consulted by a neurosurgeon. Part of the patients underwent MRI.
 Results. Out of 72 patients with appositive PCR test, 46 (63.9 %) had a severe general condition, 26 (36.1 %) had a moderate condition. The average age of patients was 71.7 years (72.2 in men and 70.9 in women). Out‑of‑hospital polysegmental pneumonia developed in 24 (33.3 %) cases. 16 (22.2 %) patients died: (23.4 % of the total number of men) and 5 (20.0 % of the total number of women). According to clinical data and CT data, ischemic stroke developed mainly in the carotid basin (50 (69.4 %) cases): in the left carotid basin (LCB) in 33 cases (45.8 %) and in the right carotid basin (RCB) in 17 cases (23.6 %). In 13 (18.1 %) cases stroke was registered in the vertebrobasilar basin (VBB). According the ST scan and anamnesis, in 6 (8.3 %) cases of accidents in the LCB there were repeated: 5 (6.9 %) — in the VBB (including: left cerebellar hemisphere, right cerebellar hemisphere, right occipital lobe) and in the RCB. In 4 (5.6 %) cases of repeated stroke in the RCB, it was transferred twice to another side of RCB, once to the LCB, and once to the VBB. In all 3 (4.2 %) cases of recurrent stroke in the VBB, it was transferred three times in the carotid basin: twice of the RCB and once to the LCB. 3 patients (4.2 %) were diagnosed with transitional ischemic attack at the VBB (all of them are middle‑aged — 36 — 43 years old). According to CT and clinical data, hemorrhagic stroke was registered in 6 patients (8.3 % of cases).
 Conclusions. Risk factors for the occurrence of HPMC against the background of COVID‑19 are the advanced age and male gender of the patients, as well as the presence of chronic cardiovascular and cerebrovascular diseases. The cases are characterized by a predominant lesion of the large vessels of the left carotid basin, repeated strokes with the appearance of a new focus in another basin, frequent deep lesions in the area of the basal nuclei, as well as background changes in brain tissue during neuroimaging examination. A severe course, complicated by lung and heart failure, prevails, especially when out‑of‑hospital polysegmental, usually bilateral, COVID‑19 pneumonia occurs.

The study of the Mongolian traditional medicine Khurtsiin deed-6 analgesic and anti-inflammatory effect by inhibiting glial cell activation in nitroglycerin-induced migraine in rats

BackgroundMigraine is a highly prevalent neurovascular disorder with complicated treatment due to multifactorial pathophysiology. During the recent years, the prevalence of migraine in Mongolia is increasing and has reached 26.5% by 2019 which indicates an increase of 5.2% over the past 10 years. The industry of traditional medicine in Mongolia has a long history of development, hence, it is evident that various herbal medicines such as but not limited to Khurtsiin deed-6 (KhD-6) can be considered as generally safe and effective against several diseases including migraine. KhD-6’s single component has shown excellent analgesic, anti-inflammatory and neuroprotective effect, while the whole compound effectiveness and molecular mechanism had not been assessed for the treatment of migraine. ObjectivesTo study the effects of Khurtsiin deed-6 compound on inflammation and neuronal cell damage in migraine model in rats. MethodsA total of 36 rats were randomly divided into the following six groups including control group, Nitroglycerin-induced (NTG-induced) migraine model group, KhD-6 groups of 50 mg/kg, 100 mg/kg and 150 mg/kg doses, and Ibuprofen (IBU) 85 mg/kg treated group. Corresponding treatments were administered intragastrically for 10 days to animals of experimental groups. Then NTG-induced migraine model group, three KhD-6 groups and IBU group were subcutaneously injected with Nitroglycerin (10mg/kg) 1 h after the last treatment. Experimental animals were observed for two hours after Nitroglycerin injection to confirm the model establishment. After four hours, all rats were anesthetized and blood was collected from three rats from each group in order to detect levels of Nitric oxide (NO), calcitonin gene-related peptide (CGRP) and endothelin (ET) by ELISA method. The remaining three animals of each experimental group were perfused under anesthesia for the removal of their brains and isolation of the trigeminal nucleus caudalis (TNC). A polymerase chain reaction (PCR) method was used to analyze OX42, COX2, RAGE, GFAP, BDNF, BAX, and Bcl expressions. ResultsNTG-induced rat migraine model presents increased NO and CGRP levels in serum as well as c-Fos expression in the brain trigeminal nucleus area, which indicates that the migraine model was successfully generated. NO and CGRP levels in serum were suppressed in KhD-6 and IBU treated groups. The c-Fos expression decreased significantly in the TNC not only in Khurtsiin-6 compound, but also in IBU treated groups. Furthermore, KhD-6 compound inhibits neuro-inflammatory pathways by reducing COX2 expression, OX42 and GFAP activation. It inhibits neuronal cell death through suppressing RAGE, BAX, Bcl expression and increasing BDNF expression. ConclusionKhD-6 offers analgesic and neuroprotective effects in the NTG-induced migraine rat model by inhibiting the activation of glial cells and the secretion of neuroinflammatory factors in the TNC region.

Modulation of the spread of pathological tau in vitro and in vivo

AbstractBackgroundIn tauopathies such as Alzheimer’s disease, tau aggregates are known to propagate across functionally connected neuronal networks, but the mechanisms underlying this process are poorly understood. Several lines of evidence support the hypothesis that tau release is dependent on neuronal activity. Pathological tau can be found in the extracellular space, inside synaptic vesicles, and other synaptic compartments, or in a free form. We aim to test both in vitro and in vivo the effect of selected botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) on the release of tau from synaptic terminals. BoNTs and TeNT enter synapses and cleave different synaptic SNARE proteins, impairing synaptic vesicle fusion and release and they may affect tau spread.MethodPrimary neurons were cultured in MFCs and transduced with lentiviruses expressing human tau (hTau) isoforms. Cells were treated with BoNTs and stimulating agents. The content of hTau in the culture media was quantified with an enzyme‐linked immunosorbent assay (ELISA). Adeno‐associated viral vectors (AAVs) expressing hTau were injected in the vitreous, and the superior colliculus (SC) and lateral geniculate nucleus (LGN) areas were analysed through immunohistochemistry.ResultThe release of the 1N4R mutant hTau (P301S), but not the wild‐type form, is affected by botulinum neurotoxin type A (BoNT/A) and neuronal stimulation, which, respectively, significantly decreases and increases the release of P301S hTau. The AAV constructs are correctly expressed in both primary neurons and in retinal ganglion cells (RGCs), and brain sections of SC and LGN were analysed.ConclusionClostridial neurotoxins represent a powerful tool for the study of neurons and synapses. Using BoNT/A, we showed that hTau release is modulated by specific SNARE complex components and differs depending on the isoform. The use of other BoNT types in both in vitro and in vivo models will help us to identify the SNARE proteins involved in tau release. This approach will provide novel insights on the mechanisms controlling tau release from synaptic terminals and identify novel molecular targets for the development of therapeutic interventions to treat tauopathies.

Effects of Feeding Frequency for Nile Tilapia Fingerlings (Oreochromis niloticus).

This study is aimed at assessing the feeding frequency for tilapia fingerlings. 240 fishes were randomly distributed in 24 containers. The feeding consisted of six frequencies: 4 (F4), 5 (F5), 6 (F6), 7 (F7), 8 (F8), and 9 (F9) times a day. The weight gain was significantly higher in F5 and F6 when compared to F4 (p = 0.0409 and 0.0306, respectively). Feed intake and apparent feed conversion did not differ between treatments (p = 0.129 and p = 0.451). About water quality, the nitrogen levels in the water from the treatments differed between F4 and F5 (p = 0.0478) and F4 and F6 (p = 0.0283) and for P between F4 and F6 (p = 0.0215) and F4 and F9 (p = 0.0432). The x 2 test showed a dependence relationship between feed frequencies and the muscle fibers frequency (p < 22 × 10-17), prevailing fibers between 10-20 micrometers in F4, F5, F6, and F7 and 30-40 in F8 and F9. The area of the hepatocytes differed only between F5 and F9, while the nucleus area did not. Partial net revenue differed in 10% between F5 and F4 (p = 0.0812) and between F6 and F4 (p = 0.0568). In conclusion, fingerlings fed 5 to 6 times a day have better zootechnical and partial recipes.

Kisspeptin-neuron control of LH pulsatility and ovulation.

Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to stimulate follicular growth, and the mid-cycle luteinising hormone (LH) surge that leads to ovulation. E2 predominantly exerts its action via oestrogen receptor-alpha (ERα), however, as gonadotrophin releasing hormone (GnRH) neurons lack ERα, E2-feedback is posited to be indirectly mediated via upstream neurons. Kisspeptin (KP) is a neuropeptide expressed in hypothalamic KP-neurons that control GnRH secretion and plays a key role in the central mechanism regulating the hypothalamic-pituitary-gonadal (HPG) axis. In the rodent arcuate (ARC) nucleus, KP is co-expressed with Neurokinin B and Dynorphin; and thus, these neurons are termed 'Kisspeptin-Neurokinin B-Dynorphin' (KNDy) neurons. ARC KP-neurons function as the 'GnRH pulse generator' to regulate GnRH pulsatility, as well as mediating negative feedback from E2. A second KP neuronal population is present in the rostral periventricular area of the third ventricle (RP3V), which includes anteroventral periventricular (AVPV) nucleus and preoptic area neurons. These RP3V KP-neurons mediate positive feedback to induce the mid-cycle luteinising hormone (LH) surge and subsequent ovulation. Here, we describe the role of KP-neurons in these two regions in mediating this differential feedback from oestrogens. We conclude by considering reproductive diseases for which exploitation of these mechanisms could yield future therapies.

Influence of alimentary deprivation on morphofunctional state of the rat's pancreas..

Literature data on the effect of alimentary deprivation (AD) on the morphological and functional changes in the pancreas, especially its exocrine part, are rare. The study of morphological changes in the exo- and endocrine pancreas of rats, after exposure to AD, was the aim of our research. Experimental rats received a diet that was reduced in weight by 30%. Access to water was free. The duration of the experiment was 28 days. Rats were decapitated under light ether anesthesia. For histological studies of the pancreas, samples were taken from its central part (body). Morphometric measurements of the gland were carried out using the computer program "Image J". It was revealed that in the exocrine pancreas of adult rats that were on AD, the area of acinus and nucleus of exocrinocytes increased, the number of nucleolus increased, the nuclear-cytoplasmic ratio and the height of the epithelium of the acinus increased. The increase in the activity of the endocrine pancreas, after exposure to AD, indicated by an increase in its following parameters: area (by 108%), number of Langerhans islets (by 34%), their size and number of endocrinocytes (by 55%). Also in the gland of these animals a decreased in the width of the layers of interlobular and interacinus connective tissue by 28%, which improves conditions for the course of metabolic processes. Thus, the effect of AD is accompanied by the appearance of morphological signs of an increased in the activity of both the exocrine and endocrine (to a greater extent) pancreas in adult rats.

Respiratory mechanics following chronic cigarette smoke exposure in the Apoe[Formula: see text] mouse model.

Even though cigarette smoking (CS) has been on the decline over the past 50 years, it is still the leading cause of preventable premature death in the United States. Preclinical models have investigated the cardiopulmonary effects of CS exposure (CSE), but the structure-function relationship in the respiratory system has not yet been fully explored. To evaluate these relationships, we exposed female apolipoprotein E-deficient (Apoe[Formula: see text]) mice to mainstream CS ([Formula: see text]) for 5 days/week over 24 weeks with room air as a control (AE, [Formula: see text]). To contextualize the impact of CSE, we also assessed the natural aging effects over 24 weeks of air exposure (baseline, [Formula: see text]). Functional assessments were performed on a small animal mechanical ventilator (flexiVent, SCIREQ), where pressure-volume curves and impedance data at four levels of positive end-expiratory pressure ([Formula: see text]) and with increasing doses of methacholine were collected. Constant phase model parameters ([Formula: see text]: Newtonian resistance, H: coefficient of tissue elastance, and G: coefficient of tissue resistance) were calculated from the impedance data. Perfusion fixed-left lung tissue was utilized for quantification of parenchyma airspace size and tissue thickness, airway wall thickness, and measurements of elastin, cytoplasm + nucleus, fibrin, and collagen content for the parenchyma and airways. Aging caused the lung to become more compliant, with an upward-leftward shift of the pressure-volume curve and a reduction in all constant phase model parameters. This was supported by larger parenchyma airspace sizes, with a reduction in cell cytoplasm + nucleus area. Airway walls became thinner, even though low-density collagen content increased. In contrast, CSE caused a downward-rightward shift of the pressure-volume curve along with an increase in H, G, and hysteresivity ([Formula: see text]). Organ stiffening was accompanied by enhanced airway hyper-responsiveness following methacholine challenge. Structurally, parenchyma airspaces enlarged, as indicated by an increase in equivalent airspace diameter ([Formula: see text]), and the septum thickened with significant deposition of low-density collagen along with an influx of cells. Airway walls thickened due to deposition of both high and low-density collagen, infiltration of cells, and epithelial cell elongation. In all, our data suggest that CSE in female Apoe[Formula: see text] mice reduces respiratory functionality and causes morphological alterations in both central and peripheral airways that results in lung stiffening, compared to AE controls.

Distribution Features and Potential Effects of Serotonin in the Cerebrum of SOD1 G93A Transgenic Mice.

Serotonin (5-HT) participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), but its effects have not been completely clarified. Therefore, we observed the distribution features and potential effects of 5-HT in the cerebrum of G93A SOD1 transgenic (TG) and wild-type (WT) mice by fluorescence immunohistochemistry, Western blotting, ELISA, as well as motor function measurements. Both 5-HT and tryptophan hydroxylase-2 (TPH2) were mainly present in the limbic systems of the cerebrum, such as the glomerular layer of the olfactory bulb, nucleus accumbens, cingulate, fimbria of the hippocampus, mediodorsal thalamic nucleus, habenular nucleus, ventromedial hypothalamus nucleus, lateral hypothalamus area, dorsal raphe nucleus, and piriform cortex. TPH2 and 5-HT were expressed in cell bodies in the dorsal raphe nucleus and piriform cortex, while in other regions they were distributed as filaments and clump shapes in axons. The TPH2 distribution in the cerebrum of TG was significantly lower than that in WT in preset, onset, and progression stages. TPH2 expression in the fimbria of the hippocampus, mediodorsal thalamic nucleus, habenular nucleus, ventromedial hypothalamus nucleus and lateral hypothalamus area was increased in the onset stage and decreased in the progression stage, gradually decreased in the cingulate with disease progression and significantly decreased in the glomerular layer of the olfactory bulb and nucleus accumbens in the onset stage in TG. The number of mammalian achaete-scute homolog-1 in the subventricular zone (SVZ) in TG was significantly lower than that in WT, which was correlated with the TPH2 distribution. Double immunofluorescence staining showed that TPH2, mammalian achaete-scute homolog-1 and 5-HT were mainly expressed in neurons but rarely expressed in microglia or astrocytes in the piriform cortex. The relative fluorescence density of TPH2 in the cingulate region was negatively correlated with the disease severity. Our findings suggest that 5-HT plays a protective role in ALS, likely by regulating neural stem cells in the subventricular zone that might be involved in neuron development in the piriform cortex.

Photolithographically Patterned Cell-Repellent PEG-b-PTHPMA Diblock Copolymer for Guided Cell Adhesion and Growth.

Surfaces for guided cell adhesion and growth are indispensable in several diagnostic and therapeutic applications. Towards this direction, four diblock copolymers comprising polyethylene glycol (PEG) and poly(2-tetrahydropyranyl methacrylate) (PTHPMA) are synthesized employing PEG macroinitiators of different chain lengths. The copolymer with a 5000Da PEG block and a PEG-PTHPMA comonomers weight ratio of 43-57 provides a film with the highest stability in the culture medium and the strongest cell repellent properties. This copolymer is used to develop a positive photolithographic material and create stripe patterns onto silicon substrates. The highest selectivity regarding smooth muscle cell adhesion and growth and the highest fidelity of adhered cells for up to 3 days in culture is achieved for stripe patterns with widths between 25 and 27.5µm. Smooth muscle cells cultured on such patterned substrates exhibit a decrease in their proliferation rate and nucleus area and an increase in their major axis length, compared to the cells cultured onto non-patterned substrates. These alterations are indicative of the adoption of a contractile rather than a synthetic phenotype of the smooth muscle cells grown onto the patterned substrates and demonstrate the potential of the novel photolithographic material and patterning method for guided cell adhesion and growth.

Pretherapeutic functional connectivity of tractography-based targeting of the ventral intermediate nucleus for predicting tremor response in patients with Parkinson's disease after thalamotomy with MRI-guided focused ultrasound.

Tractography-based direct targeting of the ventral intermediate nucleus (T-VIM) is a novel method that provides patient-specific VIM coordinates. This study aimed to explore the accuracy and predictive value of using T-VIM in combination with tractography and resting-state functional connectivity techniques to perform magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment of Parkinson's disease (PD). PD patients underwent MRgFUS thalamotomy and were recruited for functional MRI scanning. A subscore of the Clinical Rating Scale for Tremor was used to evaluate tremor improvement. T-VIM and surgical VIM (S-VIM) were defined on preoperative diffusion tensor MRI and 24-hour postoperative T1-weighted imaging, respectively. The overlapping volume and center distance between S-VIM and T-VIM were measured to determine their correlations with 12-month postoperative tremor improvement. Moreover, pretherapeutic functional connectivity of T-VIM or S-VIM, based on region-of-interest connectivity and whole-brain seed-to-voxel connectivity, was measured with the resting-state functional connectivity technique to investigate their correlations with tremor improvement. All patients had excellent tremor improvement (mean [range] tremor improvement 74.82% [50.00%-94.44%]). The authors found that both overlapping volume and center distance between T-VIM and S-VIM were significantly correlated with tremor improvement (r = 0.788 and p = 0.012 for overlapping volume; r = -0.696 and p = 0.037 for center distance). Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex (r = 0.876 and p = 0.002), subthalamic nucleus (r = 0.700 and p = 0.036), and visual area (r = 0.911 and p = 0.001) was significantly and positively correlated with tremor improvement. T-VIM may improve the clinical application of MRgFUS thalamotomy as a treatment of PD. Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex, subthalamic nucleus, and visual area may predict PD tremor responses after MRgFUS thalamotomy.