Changes In Dendritic Morphology Research Articles

Polysaccharides from Astragalus membranaceus elicit T cell immunity by activation of human peripheral blood dendritic cells

Astragalus membranaceus is a widely used herbal medicine in Asia. It has been recognized as possessing various biological properties, however, studies on the activity of the A. membranaceus polysaccharide (AMP), a major component of A. membranaceus, on human peripheral blood dendritic cells (PBDCs) have not been thoroughly investigated. In this study, we found that AMP induced changes in dendritic morphology and the upregulation of activation marker expression and inflammatory cytokine production in human blood monocyte-derived dendritic cells (MDDCs). The AMP promoted the activation of both blood dendritic cell antigen 1+ (BDCA1+) and BDCA3+ PBDCs. AMP-induced secretion of cytokines in the peripheral blood mononuclear cells (PBMCs) was mainly due to PBDCs. Finally, activated BDCA1+ and BDCA3+ PBDCs by AMP elicited proliferation and activation of autologous T cells, respectively. Hence, these data demonstrated that AMPs could activate dendritic and T cells in human blood, and may provide a new direction for the application of AMPs in the regulation of human immunity.

Effects of Caulerpa lentillifera polysaccharides on immune function in vitro and in vivo

The immune enhancement effects of Caulerpa lentillifera polysaccharides (CLP) in vitro and in vivo were observed in this study. The results of the in vitro experiments show that CLP extract can promote the activation and maturation of dendritic cells and enhance the expression of IL-6, TNF-α, CD80, CD86, and MHC II. Expression of IL-6 and TNF-α was determined with ELISA kits, CD80 and CD86 were measured by flow cytometry, and MHC II was analyzed with a laser scanning confocal microscope. Changes in dendritic cell morphology and volume were also studied. The in vivo experiment shows that CLP can promote the secretion of IL-6, INF-γ, IgA, and IgG and enhance humoral and cellular immunity in mice. CLP extract's ability to upregulate immunity in vitro and in vivo makes it worthy of further investigation as an effective natural immunopotentiator. Novelty impact statement Caulerpa lentillifera polysaccharides could enhance immunity in vitro and in vivo. C. lentillifera polysaccharides will be worthy to investigate to an natural immunopotentiator.

Investigation of correlation between the microstructural characteristics and mechanical properties of (CoCuFeNi)100-xAlx high entropy alloys

In the present study, we investigated the Al effect on the microstructure, phase, and mechanical properties of (CoCuFeNi)100-xAlx (x = 0 ∼ 20 at%) high entropy alloys (HEAs). To find out the correlation between the microstructural characterization and mechanical properties, a detailed phase and microstructural analysis was conducted through slight addition of the Al content. From Al0 to Al15 HEAs, there was no distinct change in dendritic microstructural morphology and mechanical properties. On the other hand, the B2 phase appears in the inter-dendrite region and thus (FCC1 +FCC2 +B2) multi-phase formed showing the conspicuous mechanical properties from Al15 to Al20 HEAs. Especially, Al18 HEA showed the most balanced mechanical properties due to the two-sided microstructure of (FCC+L12 +B2) and (B2 +FCC/L12). However, it was identified that the excessive Al content formed the primary B2 dendrite changing ductile to brittle deformation mode. The phase and microstructure analysis was conducted by multi-scale XRD, SEM, and TEM. Furthermore, systematic deformation mechanical analysis was carried out on deformed and fractured specimens.

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice

ABSTRACT Bacillus Calmette – Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with Alzheimer’s disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of p-JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.

Chronic exercise increases excitability of lamina X neurons through enhancement of persistent inward currents and dendritic development in mice

Chronic exercise has been shown to enhance excitability of spinal interneurons in rodents. However, the mechanisms underlying this enhancement remain unclear. In this study we investigated adaptability of lamina X neurons with 3-week treadmill exercise in mice of P21-P24. Whole-cell patch-clamp recording was performed on the interneurons from slices of T12-L4. The experimental results included the following. (1) Treadmill exercise reduced rheobase by 7.4±2.2pA (control: 11.3±6.1pA, n=12; exercise: 3.8±4.6pA, n=13; P=0.002) and hyperpolarized voltage threshold by 7.1±1.5mV (control: -36.6±4.6mV, exercise: -43.7±2.7mV; P=0.001). (2) Exercise enhanced persistent inward currents (PICs) with increase of amplitude (control: 140.6±56.3pA, n=25; exercise: 225.9±62.5pA, n=17; P=0.001) and hyperpolarization of onset voltage (control: -50.3±3.6mV, exercise: -56.5±5.5mV; P=0.001). (3) PICs consisted of dihydropyridine-sensitive calcium (Ca-PIC) and tetrodotoxin-sensitive sodium (Na-PIC) components. Exercise increased amplitude of both components but hyperpolarized onset voltage of Na-PIC only. (4) Exercise reduced derecruitment current of repetitive firing evoked by a current bi-ramp and prolonged firing in the falling phase of the bi-ramp. The derecruitment reduction was eliminated by bath application of 3μM riluzole or 25μM nimodipine, suggesting that both Na-PIC and Ca-PIC contributed to the exercise-prolonged hysteresis of firing. (5) Exercise facilitated dendritic development with significant increase in dendritic length by 285.1±113μm (control: 457.8±171.8μm, n=12; exercise: 742.9±357μm, n=14; P=0.019). We concluded that 3-week treadmill exercise increased excitability of lamina X interneurons through enhancement of PICs and increase of dendritic length. This study provided insight into cellular and channel mechanisms underlying adaptation of the spinal motor system in exercise. KEY POINTS: Chronic exercise alters adaptability of the spinal motor system in rodents; multiple mechanisms are responsible for the adaptation, including regulation of neuronal excitability and change in dendritic morphology. Spinal interneurons in lamina X are a cluster of heterogeneous neurons playing multifunctional roles in the spinal cord; chronic exercise in juvenile mice increased excitability of these interneurons and facilitated dendritic development. Lamina X neurons expressed persistent inward currents (PICs) with calcium (Ca-PIC) and sodium (Na-PIC) components; the exercise-increased excitability of lamina X neurons was mediated by enhancing the Ca-PIC and Na-PIC components and increasing dendritic length. This study unveiled novel morphological and ionic mechanisms underlying adaptation of lamina X neurons in rodents during chronic exercise.

Armadillo regulates nociceptive sensitivity in the absence of injury.

Abnormal pain has recently been estimated to affect ∼50 million adults each year within the United States. With many treatment options for abnormal pain, such as opioid analgesics, carrying numerous deleterious side effects, research into safer and more effective treatment options is crucial. To help elucidate the mechanisms controlling nociceptive sensitivity, the Drosophila melanogaster larval nociception model has been used to characterize well-conserved pathways through the use of genetic modification and/or injury to alter the sensitivity of experimental animals. Mammalian models have provided evidence of β-catenin signaling involvement in neuropathic pain development. By capitalizing on the conserved nature of β-catenin functions in the fruit fly, here we describe a role for Armadillo, the fly homolog to mammalian β-catenin, in regulating baseline sensitivity in the primary nociceptor of the fly, in the absence of injury, using under- and over-expression of Armadillo in a cell-specific manner. Underexpression of Armadillo resulted in hyposensitivity, while overexpression of wild-type Armadillo or expression of a degradation-resistant Armadillo resulted in hypersensitivity. Neither underexpression nor overexpression of Armadillo resulted in observed dendritic morphological changes that could contribute to behavioral phenotypes observed. These results showed that focused manipulation of Armadillo expression within the nociceptors is sufficient to modulate baseline response in the nociceptors to a noxious stimulus and that these changes are not shown to be associated with a morphogenetic effect.

Fluoxetine exposure throughout neurodevelopment differentially influences basilar dendritic morphology in the motor and prefrontal cortices

The significance of serotonin (5HT) in mental health is underscored by the serotonergic action of many classes of psychiatric medication. 5HT is known to have a significant role in neurodevelopment, thus 5HT disruption during development may have a long term impact on brain structure and circuits. We previously generated a model of 5HT alteration throughout neurodevelopment by maternal administration of the selective serotonin reuptake inhibitor fluoxetine. We found resulting social behavior alterations in the offspring during both postnatal and adult ages. Previous work by others has indicated that early 5HT disruption influences neuronal morphology. Therefore, in the current study we sought to determine if dendritic morphological changes occur in areas involved in the social behavior deficits we previously observed, specifically the primary motor (M1) and medial prefrontal (mPFC) cortices. We quantified dendritic morphology of projection neurons in M1 and mPFC at postnatal day (P)10 and P79 in mice exposed to fluoxetine. Basilar dendritic complexity and spine density were persistently decreased in M1 fluoxetine-exposed neurons while in the mPFC, similar reductions were observed at P79 but were not present at P10. Our findings underscore that the developing brain, specifically the projection cortex, is vulnerable to 5HT system perturbation, which may be related to later behavioral disruptions.

Age and intraocular pressure in murine experimental glaucoma.

Age and intraocular pressure (IOP) are the two most important risk factors for the development and progression of open-angle glaucoma. While IOP is commonly considered in models of experimental glaucoma (EG), most studies use juvenile or adult animals and seldom older animals which are representative of the human disease. This paper provides a concise review of how retinal ganglion cell (RGC) loss, the hallmark of glaucoma, can be evaluated in EG with a special emphasis on serial in vivo imaging, a parallel approach used in clinical practice. It appraises the suitability of EG models for the purpose of in vivo imaging and argues for the use of models that provide a sustained elevation of IOP, without compromise of the ocular media. In a study with parallel cohorts of adult (3-month-old, equivalent to 20 human years) and old (2-year-old, equivalent to 70 human years) mice, we compare the effects of elevated IOP on serial ganglion cell complex thickness and individual RGC dendritic morphology changes obtained in vivo. We also evaluate how age modulates the impact of elevated IOP on RGC somal and axonal density in histological analysis as well the density of melanopsin RGCs. We discuss the challenges of using old animals and emphasize the potential of single RGC imaging for understanding the pathobiology of RGC loss and evaluating new therapeutic avenues.

Induction of Bdnf from promoter I following electroconvulsive seizures contributes to structural plasticity in neurons of the piriform cortex

BackgroundElectroconvulsive therapy (ECT) efficacy is hypothesized to depend on induction of molecular and cellular events that trigger neuronal plasticity. Investigating how electroconvulsive seizures (ECS) impact plasticity in animal models can help inform our understanding of basic mechanisms by which ECT relieves symptoms of depression. ECS-induced plasticity is associated with differential expression of unique isoforms encoding the neurotrophin, brain-derived neurotrophic factor (BDNF). HypothesisWe hypothesized that cells expressing the Bdnf exon 1-containing isoform are important for ECS-induced structural plasticity in the piriform cortex, a highly epileptogenic region that is responsive to ECS. MethodsWe selectively labeled Bdnf exon 1-expressing neurons in mouse piriform cortex using Cre recombinase dependent on GFP technology (CRE-DOG). We then quantified changes in dendrite morphology and density of Bdnf exon 1-expressing neurons. ResultsLoss of promoter I-derived BDNF caused changes in spine density and morphology in Bdnf exon 1-expressing neurons following ECS. ConclusionsPromoter I-derived Bdnf is required for ECS-induced dendritic structural plasticity in Bdnf exon 1-expressing neurons.

Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits

Hypobaric hypoxia (HH) is a typical characteristic of high altitude environment and causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction and cognitive retardation. Here, we sought to understand the mechanisms underlying cognitive deficits under HH exposure. Our results showed that hypobaric hypoxia exposure impaired cognitive function and suppressed dendritic spine density accompanied with increased neck length in both basal and apical hippocampal CA1 region neurons in mice. The expression of PSD95, a vital synaptic scaffolding molecule, is down-regulated by hypobaric hypoxia exposure and post-transcriptionally regulated by cold-inducible RNA-binding protein (Cirbp) through 3′-UTR region binding. PSD95 expressing alleviates hypoxia-induced dendritic spine morphology changes of hippocampal neurons and memory deterioration. Moreover, overexpressed Cirbp in hippocampus rescues HH-induced abnormal expression of PSD95 and attenuates hypoxia-induced dendritic spine injury and cognitive retardation. Thus, our findings reveal a novel mechanism that Cirbp-PSD-95 axis appears to play an essential role in HH-induced cognitive dysfunction in mice.

Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability.

Patients with monoallelic bromodomain and PHD finger-containing protein 1 (BRPF1) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that Brpf1 was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse Brpf1 plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of Brpf1 knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down Brpf1 in vivo and examined the learning and memory ability by Morris water maze. We found that mild knockdown of Brpf1 reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that Brpf1 mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as C1ql1, Gpr17, Htr1d, Glra1, Cxcl10, and Grin2a) were dysregulated upon Brpf1 knockdown. Our results showed that Brpf1 mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with BRPF1 mutations.

Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription.

Sulforaphane (SFN) is an organic isothiocyanate and an NF-E2-related factor-2 (Nrf2) inducer that exerts prophylactic effects on depression-like behavior in mice. However, the underlying mechanisms remain poorly understood. Brain-derived neurotrophic factor (BDNF), a neurotrophin, is widely accepted for its antidepressant effects and role in stress resilience. Here, we show that SFN confers stress resilience via BDNF upregulation and changes in abnormal dendritic spine morphology in stressed mice, which is accompanied by rectifying the irregular levels of inflammatory cytokines. Mechanistic studies demonstrated that SFN activated Nrf2 to promote BDNF transcription by binding to the exon I promoter, which is associated with increased Nrf2, and decreased methyl-CpG binding protein-2 (MeCP2), a transcriptional suppressor of BDNF, in BV2 microglial cells. Furthermore, SFN inhibited the pro-inflammatory phenotype and activated the anti-inflammatory phenotype of microglia, which was associated with increased Nrf2 and decreased MeCP2 expression in microglia of stressed mice. Hence, our findings support that Nrf2 induces BDNF transcription via upregulation of Nrf2 and downregulation of MeCP2 in microglia, which is associated with changes in the morphology of damaged dendritic spines in stressed mice. Meanwhile, the data presented here provide evidence for the application of SFN as a candidate for the prevention and intervention of depression.

Longitudinal In Vivo Changes in Retinal Ganglion Cell Dendritic Morphology After Acute and Chronic Optic Nerve Injury.

PurposeTo characterize in vivo dendritic changes in retinal ganglion cells (RGCs) after acute (optic nerve transection, ONT) and chronic (experimental glaucoma, EG) optic nerve injury.MethodsONT and EG (microbead model) were carried out in Thy1-YFP mice in which the entire RGC dendritic arbor was imaged with confocal fluorescence scanning laser ophthalmoscopy over two weeks in the ONT group and over two and six months, respectively, in two (groups 1 and 2) EG groups. Sholl analysis was used to quantify dendritic structure with the parameters: area under the curve (AUC), radius of the dendritic field, peak number of intersections (PI), and distance to the PI (PD).ResultsDendritic changes were observed after three days post-ONT with significant decreases in all parameters at two weeks. In group 1 EG mice, mean (SD) intraocular pressure (IOP) was 15.2 (1.1) and 9.8 (0.3) mmHg in the EG and untreated contralateral eyes, respectively, with a significant corresponding decrease in AUC, PI, and PD, but not radius. In group 2 mice, the respective IOP was 13.1 (1.0) and 8.8 (0.1) mmHg, peaking at two months before trending towards baseline. Over the first two months, AUC, PI, and PD decreased significantly, with no further subsequent changes. The rates of change of the parameters after ONT was 5 to 10 times faster than in EG.ConclusionsRapid dendritic changes occurred after ONT, while changes in EG were slower and associated with level of IOP increase. The earliest alterations were loss of inner neurites without change in dendritic field.

CA Modeling of Microsegregation and Growth of Equiaxed Dendrites in the Binary Al-Mg Alloy.

A two-dimensional model based on the Cellular Automaton (CA) technique for simulating free dendritic growth in the binary Al + 5 wt.% alloy was presented. In the model, the local increment of the solid fraction was calculated using a methodology that takes into account changes in the concentration of the liquid and solid phase component in the interface cells during the solidification transition. The procedure of discarding the alloy component to the cells in the immediate vicinity was used to describe the initial, unstable dendrite growth phase under transient diffusion conditions. Numerical simulations of solidification were performed for a single dendrite using cooling rates of 5 K/s, 25 K/s and 45 K/s and for many crystals assuming the boundary condition of the third kind (Newton). The formation and growth of primary and secondary branches as well as the development of component microsegregation in the liquid and solid phase during solidification of the investigated alloy were analysed. It was found that with an increase in the cooling rate, the dendrite morphology changes, its cross-section and the distance between the secondary arms decrease, while the degree of component microsegregation and temperature recalescence in the initial stage of solidification increase. In order to determine the potential of the numerical model, the simulation results were compared with the predictions of the Lipton-Glicksman-Kurz (LGK) analytical model and the experimental solidification tests. It was demonstrated that the variability of the dendrite tip diameter and the growth rate determined in the Cellular Automaton (CA) model are similar to the values obtained in the LGK model. As part of the solidification tests carried out using the Derivative Differential Thermal Analysis (DDTA) method, a good fit of the CA model was established in terms of the shape of the solidification curves as well as the location of the characteristic phase transition temperatures and transformation time. Comparative tests of the real structure of the Al + 5 wt.% Mg alloy with the simulated structure were also carried out, and the compliance of the Secondary Dendrite Arm Spacing (SDAS) parameter and magnesium concentration profiles on the cross-section of the secondary dendrites arms was assessed.

Chronic opipramol treatment extinguishes cocaine craving through Rac1 in responders: A rat model study.

Ras-related C3 botulinum toxin substrate 1 (Rac1), of the Rho small GTPase family, is a key regulator of actin cytoskeleton rearrangement and plays an important role in dendritic morphogenesis. Cocaine produces neuronal alterations, including structural changes in dendritic number and morphology. Emerging data indicate sigma-1 receptors (σ-1Rs) as a promising candidate for the prevention of cocaine craving. Opipramol is a σ-1R agonist approved in some European countries for depression and anxiety. Here we report that opipramol, mediated by Rac1, attenuates cocaine-seeking behavior in a rat model of self-administration. The opipramol effect was shown in two phases. It decreased cocaine-seeking behavior throughout the withdrawal phase and, interestingly, showed a significant reduction of cocaine-primed reinstatement in 75% of the opipramol-treated group (termed 'responders'). All opipramol-treated rats showed a decrease in σ-1R mRNA expression levels in the nucleus accumbens (NAc) versus controls. Responders also exhibited significantly decreased NAc Rac1 mRNA expression levels, compared with non-responder rats. Hence, Rac1 differentiated responders from non-responders. Rac1 correlated positively with σ-1R mRNA levels in opipramol responders. In another experiment, Rac1 inhibitor injected directly into the NAc core decreased active lever presses on the first day of extinction, indicating the critical role of Rac1 in the opipramol effect on drug seeking. We postulate that chronic activation of σ-1R, through a dynamic interaction with Rac1, may suggest a new approach to treat substance use disorder (SUD). Rac1 inhibition is a prerequisite for decreasing drug seeking and rehabilitation, and this can be achieved by opipramol, a medication that can be given during detoxification.

Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms

BackgroundKetamine elicits rapid onset antidepressant effects in patients with clinical depression through mechanisms hypothesized to involve the genesis of neocortical dendritic spines and synapses. Yet, the observed changes in dendritic spine morphology usually emerge well after ketamine clearance, raising questions about the link between rapid behavioral effects of ketamine and plasticity. MethodsHere, we used two-photon glutamate uncaging/imaging to focally induce spinogenesis in the medial prefrontal cortex, directly interrogating baseline and ketamine-associated plasticity of deep layer pyramidal neurons in C57BL/6 mice. We combined pharmacological, genetic, optogenetic, and chemogenetic manipulations to interrogate dopaminergic mechanisms underlying ketamine-induced rapid enhancement in evoked plasticity and associated behavioral changes. ResultsWe found that ketamine rapidly enhances glutamate-evoked spinogenesis in the medial prefrontal cortex, with timing that matches the onset of its behavioral efficacy and precedes changes in dendritic spine density. Ketamine increases evoked cortical spinogenesis through dopamine Drd1 receptor (Drd1) activation that requires dopamine release, compensating blunted plasticity in a learned helplessness paradigm. The enhancement in evoked spinogenesis after Drd1 activation or ketamine treatment depends on postsynaptic protein kinase A activity. Furthermore, ketamine’s behavioral effects are blocked by chemogenetic inhibition of dopamine release and mimicked by activating presynaptic dopaminergic terminals or postsynaptic Gαs-coupled cascades in the medial prefrontal cortex. ConclusionsOur findings highlight dopaminergic mediation of rapid enhancement in activity-dependent dendritic spinogenesis and behavioral effects induced by ketamine.

Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice

Synapse or dendritic spine loss is the strongest correlate of cognitive decline in Alzheimer’s disease (AD), and neurofibrillary tangles (NFTs), but not amyloid-β plaques, associate more closely with transition to mild cognitive impairment. Yet, how dendritic spine architecture is affected by hyperphosphorylated tau is still an ongoing question. To address this, we combined cell and biochemical analyses of the Tau P301S mouse line (PS19). Individual pyramidal neurons in the hippocampus and medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D morphometry analysis. In the hippocampus, PS19 mice and non-transgenic (NTG) littermates displayed equivalent spine density at 6 and 9 months, but both genotypes exhibited age-related thin spine loss. PS19 mice exhibited significant increases in synaptic tau protein levels and mean dendritic spine head diameter with age. This suggests that CA1 pyramidal neurons in PS19 mice may undergo spine remodeling in response to tau accumulation and age. In the mPFC, spine density was similar among PS19 mice and NTG littermates at 6 and 9 months, but age-related reductions in synaptic tau levels were observed among PS19 mice. Collectively, these studies reveal brain region-specific changes in dendritic spine density and morphology in response to age and the presence of hyperphosphorylated tau in the PS19 mouse line.

ALS-CSF-induced structural changes in spinal motor neurons of rat pups cause deficits in motor behaviour.

Amyotrophic lateral sclerosis (ALS) is a late-onset, neurodegenerative disease associated with the loss of motor neurons in the spinal cord, brain stem and primary motor cortex. Deficit in the motor function is one of the clinical features of this disease. However, the association between adverse morphological alterations in the spinal motor neurons and motor deficit in sporadic ALS (SALS) is still debated. The present study has sought to investigate the effects of serial intrathecal injections of ALS-CSF into rat pups, at post-natal (P) days 3, 9 and 14, on the motor neuronal (MN) morphology at the cervical and lumbar levels of the spinal cord at P16 and P22. The present study used Cresyl violet and Golgi-Cox staining methods to determine the progressive changes in the morphology of spinal MNs in both cervical and lumbar extensions. The study found a loss of motor neurons in the spinal cord (36% for P16 in cervical and 41.7% in P16 lumbar and 49.57% for P22 cervical and 44.63% for P22 lumbar) and reduced choline acetyl transferase (ChAT) expression after repeated infusion of ALS-CSF. Significant increase in the soma area was also found in ALS-CSF rats (around 21% in P22 cervical and 26.4% in P22 lumbar). Soma hypertrophy was associated with increased dendritic arborization of MNs at both cervical and lumbar levels of the spinal cord. The data also showed a direct correlation between ALS-CSF induced changes in the MN number in the spinal cord and motor behavioral deficits. The loss of MNs, reduced ChAT, changes in soma and dendritic morphology with declined rotarod performance, thus, confirming the pathological phenotypes as seen in ALS patients.

VEGF-D Downregulation in CA1 Pyramidal Neurons Exerts Asymmetric Changes of Dendritic Morphology without Correlated Electrophysiological Alterations

The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells. Lack of VEGF-D resulted in long-term memory deficits, suggesting a link between dendritic morphology and cognitive function. Here, we compared the effect of VEGF-D expression on basal versus apical dendrites of CA1 pyramidal cells, as well as its importance for synaptic processing of network oscillations. We report opposing, layer-specific effects of VEGF-D knockdown which resulted in shrinkage of basal and increased complexity of apical dendrites. Synaptic potentials and layer-specific voltage gradients during network oscillations remained, however, unaltered. These findings reveal a high spatial selectivity of VEGF-D effects at the sub-cellular level, and strong homeostatic mechanisms which keep spatially segregated synaptic inputs in a balance.

Thermal stability, microstructure and texture evolution of thermomechanical processed AlCoCrFeNi2.1 eutectic high entropy alloy

The microstructural and texture evolutions of as-cast AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) have been investigated in the course of thermomechanical processing at the temperature range of 25–500 °C. Interestingly, compared with other conventional casting structures, significant strength-ductility ratio has been achieved at room temperature. In addition, the volume fractions of the constituent phases: soft FCC (face-centered cubic), and the hard BCC (body-centered cubic) phases, do not significantly change from room to elevated deformation temperatures. In fact, the strength and ductility have not been decreased at higher temperatures which represent the mechanical stability of the alloy in the examined temperature range. From room temperature up to 300 °C, the dendrites have been stretched and broken with a slight deviation from the load direction, whereas at higher temperature of 500 °C the dendrites have been rotated relative to the direction of load before fracture. Texture examination reveals the formation of a random texture in the initial and deformed states due to simultaneous contribution of different influencing factors such as stretching of dendrites during deformation, the dendrite morphology changes, and the presence of hard and soft phases and their interaction with each other.