Differences In Spine Morphology Research Articles

Microanatomical study of pyramidal neurons in the contralesional somatosensory cortex after experimental ischemic stroke.

At present, many studies support the notion that after stroke, remote regions connected to the infarcted area are also affected and may contribute to functional outcome. In the present study, we have analyzed possible microanatomical alterations in pyramidal neurons from the contralesional hemisphere after induced stroke. We performed intracellular injections of Lucifer yellow in pyramidal neurons from layer III in the somatosensory cortex of the contralesional hemisphere in an ischemic stroke mouse model. A detailed 3-dimensional analysis of the neuronal complexity and morphological alterations of dendritic spines was then performed. Our results demonstrate that pyramidal neurons from layer III in the somatosensory cortex of the contralesional hemisphere show selective changes in their dendritic arbors, namely, less dendritic complexity of the apical dendritic arbor-but no changes in the basal dendritic arbor. In addition, we found differences in spine morphology in both apical and basal dendrites comparing the contralesional hemisphere with the lesional hemisphere. Our results show that pyramidal neurons of remote areas connected to the infarct zone exhibit a series of selective changes in neuronal complexity and morphological distribution of dendritic spines, supporting the hypothesis that remote regions connected to the peri-infarcted area are also affected after stroke.

Effect of AMPKα2 knockdown on Alzheimer's pathogenesis and cognitive deficits in young Tg19959 mice.

AMP-activated protein kinase (AMPK) is a cellular energy censor that has been implicated in Alzheimer's disease (AD). The catalytic α isoforms (α1 and α2) of AMPK are normally expressed in a homeostatic equilibrium but are differentially expressed in AD brains, with α2 expression significantly decreased compared to controls. AMPK dysregulation may be an early feature of AD that promotes accelerated cognitive decline through its roles in protein synthesis regulation, metabolism, autophagy, and mitochondrial biogenesis. The early loss of the α2 isoform may exacerbate or accelerate disease progression in the preclinical stage. AMPKα2 was conditionally knocked down in excitatory forebrain neurons in the Tg19959 AD mouse model to create a heterozygous AMPKα2/Tg19959 double mutant. At 3-5 months of age, before cognitive impairments become evident, the mice were subjected to the Morris Water Maze (MWM) and Novel Object Recognition (NOR) task that measures hippocampus-dependent spatial learning and memory. In addition, Golgi staining, immunohistochemistry, and transmission electron microscopy of the hippocampus were performed. The double mutant AMPKα2/Tg19959 mice showed significant memory impairments in both the MWM and NOR task compared to wild type, Tg19959, and α2/Cre littermates. The AMPKα2/Tg19959 double mutant mice also showed significant decreases in post-synaptic density size and in the number of polyribosomes. Differences in spine morphology and amyloid plaque deposition were also observed. AMPKα2 knockdown in a "pre-symptomatic" AD mouse model leads to accelerated cognitive deficits and disruption of protein synthesis regulatory mechanisms. Taken together, these findings suggest that reduction of AMPKα2 may exacerbate or accelerate cognitive decline and AD pathogenesis. This finding could provide a future therapeutic target for the treatment of AD.

Maternal sleep disordered breathing during pregnancy as a cause of autism relevant neuronal and behavioral aberrations in the offspring.

Sleep disordered breathing (SDB) is characterized by recurring breathing cessations during sleep, causing intermittent hypoxia (oxygen deprivation) often several hundred times per night. SDB is present in ~15% of pregnant women as compared to ~2–4% of non‐pregnant women of childbearing age. Risk factors for gestational SDB development bear striking similarities to the collection of maternal risk factors for autism spectrum disorders (ASD), including advanced maternal age and maternal obesity. Maternal immune activation/inflammation is both a consequence of SDB, and an independent risk factor for, ASD. We posit that an overlooked, yet increasingly common inflammatory stimulus, maternal SDB, contributes to ASD etiology. We recently developed a rat model in which to study the consequences of maternal SDB on the offspring by exposing pregnant rats to nightly intermittent hypoxia from gestational days 10–21. Our findings indicate that offspring of mothers subjected to intermittent hypoxia during pregnancy exhibit deficits in several autism‐relevant behaviors, including a constellation of cognitive impairments, reduced interest in social interaction, and heightened anxiety. In most instances, the magnitude of behavioral disruption was more severe in male than female offspring. To begin to understand the mechanisms contributing to these behavioral aberrations, we examined the density of dendritic spines in the prefrontal cortex (PFC) and CA3 region of the hippocampus. Our data suggest that the offspring of mothers subjected to nightly intermittent hypoxia exhibited a striking increase in dendritic spine density in the PFC when compared to control offspring. However, the dendritic spine density in the CA3 region showed no significant differences between groups. Similar to our behavioral observations, dendritic spine aberrations were more prominent in male vs. female offspring. Additionally, these male offspring showed significant differences in spine morphology when compared to control offspring. Taken together, these findings indicate that maternal sleep disordered breathing not only induces autism‐relevant behavioral impairments, but also mimics the heightened cortical synaptic connectivity phenotypes recently uncovered in autism. Future studies are aimed at identifying a role for microglial inflammation and concomitant reduction in microglial‐mediated synaptic pruning in the behavioral and synaptic structural alterations that we have revealed in this model.Support or Funding InformationR25 Team‐ScienceUW2020 Pilot Award

Malunion of post-traumatic thoracolumbar fractures.

Thoracolumbar malunion is the result of loss of correction, insufficient correction or even no correction (both in the frontal and sagittal planes) of a thoracolumbar fracture. The main causes are incorrect assessment of the fracture's complexity (burst fracture), its potential progression to kyphosis and associated disc or ligament damage. It can also be the result of a poorly conducted initial treatment. The types of malunion have changed over the years because of the introduction of vertebroplasty and kyphoplasty. The malunion can be well tolerated if there is only a moderate deformity. However, the functional and pain-related limitations can be severe with large deformities. Functional limitation is mainly related to sagittal imbalance, but also to sequelae associated with the injury in various ways (non-union, disc degeneration, spinal cord compression, syringomyelia, etc.). The deformity and its consequences are evaluated globally using full-body standing radiographs (EOS), CT scan and MRI. Comparison of MRI images taken in a lying position to weight bearing views or even dynamic ones is an additional means to evaluate whether the lesions are reducible. Differences in spine morphology and compensatory mechanisms to combat the sagittal imbalance induced by the deformity must also be analyzed. These provide more complete information about the consequences of the malunion and help to establish the best corrective strategy. These compensatory mechanisms consist of accentuation of lumbar lordosis along with reduction of thoracic kyphosis. As a last resort, the pelvis and femur contribute to this compensation when there is a large deformity or a stiff spine due to preexisting osteoarthritis. Treatment strategies are fairly well standardized. When the deformity is reducible, a two-stage surgery is indicated. When the deformity is not reducible, posterior transpedicular closed wedge osteotomy is the gold standard. Nevertheless, the best way to treat thoracolumbar malunion is to prevent it.

Biomechanical Modeling of Spine Flexibility and Its Relationship to Spinal Range of Motion and Idiopathic Scoliosis

Study designCross-sectional. ObjectiveTo examine the relationships between spine morphology, spine flexibility, and idiopathic scoliosis. BackgroundGirls have a higher incidence of clinically significant scoliosis than boys, along with smaller vertebrae and greater flexibility. Based on biomechanical modeling, we hypothesized that smaller vertebral width relative to intervertebral disc (IVD) height would be associated with both greater lateral flexibility of the spine and with idiopathic scoliosis. MethodsMagnetic resonance imaging was used to measure IVD height, vertebral width, and paraspinous musculature in 22 girls with mild and moderate idiopathic scoliosis and 29 girls without scoliosis ages 9–13 years. Clinical measurement of maximum lateral bending was also performed in the girls without scoliosis. A simple biomechanical model was used to estimate bending angle from the ratio of IVD height to vertebral half-width for L1–L4. The average ratio (Ravg) and calculated total bending angle (αtot) for L1–L4 were compared to the clinical measurements of lateral bending flexibility in the control group. These measures were also compared between the scoliosis and control groups. ResultsThere was a significant positive relationship between clinical flexibility and both Ravg (p = .041) and αtot (p = .042) adjusting for skeletal age, height, body mass index, and paraspinous muscle area as covariates. The ratio was significantly higher (Ravg = 0.45 vs. 0.38, p < .0001) and the bending angle was significantly greater (αtot = 107° vs. 89°, p < .0001) for girls with scoliosis compared with controls. ConclusionThese results suggest that differences in spine morphology and corresponding changes in spine flexibility may be related to idiopathic scoliosis. If these relationships can be corroborated in larger prospective studies, these easily measured morphologic traits may contribute to a better understanding of the etiology of idiopathic scoliosis and an improved ability to predict scoliosis progression. Level of EvidenceLevel III.

Upper spine morphology in hypophosphatemic rickets and healthy controls: a radiographic study

The aim of this study was to describe upper spine morphology in adult patients with hypophosphatemic rickets (HR) compared with controls to assess differences in spine morphology in terms of severity of skeletal impact and to study associations between spine morphology and craniofacial morphology. The study population comprised 36 HR patients and 49 controls. The atlas and axis dimensions were measured on cephalograms, and the differences between the groups were estimated by regression analysis. The upper spine morphology was visually assessed to estimate the prevalence of cervical vertebral anomalies. The dimensions of the atlas and the axis were larger in HR patients than in controls (P ≤ 0.001), and fusions (FUS) occurred more often in HR patients (39%) than in controls (6%; P ≤ 0.001). In HR patients, the length of the atlas correlated positively (P = 0.008) and the height of the dens correlated negatively (P = 0.043) with the severity of skeletal impact. The height of the posterior arch of the atlas and the length of the axis correlated negatively with the cranial base angle (P ≤ 0.017), and the vertical dimensions of the atlas correlated positively with the thickness of the occipital skull (P ≤ 0.015). The length of the atlas correlated positively with mandibular prognathism (P = 0.042). FUS correlated positively with the frontal and parietal thickness (P = 0.034 and P = 0.003, respectively). The dimension of the atlas and the axis and the prevalence of the FUS were increased in HR patients compared with controls. Upper spine dimensions were associated with craniofacial dimensions, primarily in relation to the posterior cranial fossa.

Sampling issues in quantitative analysis of dendritic spines morphology

BackgroundQuantitative analysis of changes in dendritic spine morphology has become an interesting issue in contemporary neuroscience. However, the diversity in dendritic spine population might seriously influence the result of measurements in which their morphology is studied. The detection of differences in spine morphology between control and test group is often compromised by the number of dendritic spines taken for analysis. In order to estimate the impact of dendritic spine diversity we performed Monte Carlo simulations examining various experimental setups and statistical approaches. The confocal images of dendritic spines from hippocampal dissociated cultures have been used to create a set of variables exploited as the simulation resources.ResultsThe tabulated results of simulations given in this article, provide the number of dendritic spines required for the detection of hidden morphological differences between control and test groups in terms of spine head-width, length and area. It turns out that this is the head-width among these three variables, where the changes are most easily detected. Simulation of changes occurring in a subpopulation of spines reveal the strong dependence of detectability on the statistical approach applied. The analysis based on comparison of percentage of spines in subclasses is less sensitive than the direct comparison of relevant variables describing spines morphology.ConclusionsWe evaluated the sampling aspect and effect of systematic morphological variation on detecting the differences in spine morphology. The results provided here may serve as a guideline in selecting the number of samples to be studied in a planned experiment. Our simulations might be a step towards the development of a standardized method of quantitative comparison of dendritic spines morphology, in which different sources of errors are considered.

Calcium from internal stores modifies dendritic spine shape.

Since their discovery at the turn of the century by Ramon y Cajal (1), dendritic spines have fascinated scientists by their unusual structure and by their likely role in cognitive functions such as learning and memory. Spines are protrusions from dendrites having diverse shapes that range more than 100-fold in size. Larger spines have proportionately larger synapses and more diversity in subcellular organelles and molecular composition than do smaller spines. These differences in spine morphology and composition might account for differences in the function of the synapses located on them. Existing data suggest that spines are maintained by optimal activation. More spines form when neurons have less excitatory activation, and spines are lost when activation is too high, or when presynaptic axons degenerate (for review, see ref. 2). This pattern suggests that neurons may homeostatically regulate input by means of the number of axospinous synapses.

Classification of Screwworms (Diptera: Calliphoridae) by Larval Spine Morphology

The morphology of screwworm, Cochliomyia hominivorax (Coquerel), larval spines was affected by larval substrate and geographic effects on variation. Spine morphology of individual larvae was used to determine criteria for discrimination analysis classification. Classification criteria for types of wounds and host species were determined for larvae from central and southern Mexico. Larvae from marginal populations (United States, Caribbean Islands, Costa Rica) were classified by these criteria. Classifications were 27% accurate for wound type and 20% correct for animal species. When single egg masses were split and larvae were reared on laboratory diet and animal substrates, analysis of spine types showed significant rearing environment and sibship (egg mass) effects. Cluster analysis of geographic groups showed that larvae from central populations were closely clustered, whereas marginal groups were morphologically dissimilar from each other and from the central populations. These results indicate that larval spine morphology has limited value in taxonomic or systematic studies of screwworms and that mating compatibility was not related to spine similarity among populations. The significant differences between wound-reared and artificial media-reared larvae indicate that differences in spine morphology could be used to verify that samples from the field were indeed taken from animal wounds.