RAB39B-mediated trafficking of the GluA2-AMPAR subunit controls dendritic spine maturation and intellectual disability-related behaviour

Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson’s disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca2+-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice. The persistence of immature circuits is triggered by increased hypermobility of the spine, which is restored by the Ca2+-permeable AMPAR antagonist NASPM. Together, these data confirm that RAB39B controls AMPAR trafficking, which in turn plays a pivotal role in neuronal dendritic spine remodelling and that targeting Ca2+-permeable AMPARs may highlight future pharmaceutical interventions for RAB39B-associated disease conditions.

O Diagnóstico da Raquialgia no Atleta Jovem – uma Revisão Bibliográfica

Back pain in the young athlete is as frequent as its diagnosis is challenging due to the multiplicity of diagnostic hypotheses. Although most cases are based on poor mechanics and muscle strains, not all are innocent or self-limited. The physician must know the anatomical and physiological characteristics of immature spine, as well as the sport-specific injuries. It is imperative to obtain a complete clinical history and a complete physical exam, including neurological examination and specific provocative tests. After finding the pathology, proper treatment can help the patient returning safely to sports activity.

A pilot study of influence of pedicle screw instrumentation on immature vertebra: a minimal 5-year follow-up in children younger than 5 years

OBJECTIVEConcerns remain over the influence of pedicle screw instrumentation on the growth potential of an immature spine. Previous studies have reported discrepancies between animal experiments and clinical studies. The authors’ objective was to explore the influence of pedicle screw instrumentation on the growth of an immature spine at a very young age.METHODSIndividuals who met the authors’ criteria were included. Anteroposterior diameter of the vertebral body; pedicle length on both sides; and anteroposterior diameter, transverse diameter, and area of the spinal canal were measured on CT images before surgery and at the final follow-up. Parameters of instrumented vertebrae and adjacent noninstrumented vertebrae were compared. The growth value and growth percentage of each parameter were calculated. Subgroup comparisons were made in thoracic vertebrae and lumbar vertebrae. Statistical analyses were performed.RESULTSThirteen patients with a congenital spinal deformity were included in the study. The average age at surgery was 3.4 (range 2–5) years, and the average follow-up was 7.2 (range 5–11) years. Osteotomy and short instrumentation with pedicle screws were performed in each case. A total of 69 segments were measured, including 43 instrumented vertebrae and 26 immediately adjacent noninstrumented vertebrae. Significant increases in all parameters were noted at the final follow-up. In instrumented vertebrae, growth of the pedicle length and the anteroposterior diameter and area of the spinal canal increased significantly, while growth of the anteroposterior diameter of the vertebral body decreased significantly compared with noninstrumented vertebrae. Similar results were noted in the lumbar region. The shape-change phenomenon was found in noninstrumented vertebrae but was not apparent in instrumented vertebrae.CONCLUSIONSPedicle screw instrumentation may slow down growth of the vertebral body, indirectly speed up growth of the spinal canal, and hinder the shape-change phenomenon of the lumbar spinal canal. However, the influences were quite slight, and significant development did occur in instrumented vertebrae. Therefore, pedicle screw instrumentation may not have much effect on the growth of immature vertebrae in children younger than 5 years.

Synaptic m6A Epitranscriptome Reveals Functional Partitioning of Localized Transcripts for Dynamic Tripartite Synapse Modulation

A localized transcriptome at the synapse facilitates synapse-, stimulus-, and transcript-specific synthesis of the local proteome in response to neuronal activity. While enzyme-mediated mRNA modifications have been shown to regulate cellular mRNA turnover and translation, the role of these modifications in regulating synaptic RNA has not been studied. We established low-input m6A-seq of synaptosomal RNA to determine the chemically modified local transcriptome in healthy adult mouse forebrain and identified 4,329 selectively enriched m6A RNA peaks in 2,987 genes, which we refer to as the synaptic m6A epitranscriptome (SME). SME is functionally enriched in synthesis and modulation of tripartite synapses, and in pathways implicated in neurodevelopmental and neuropsychiatric diseases. Interrupting m6A-mediated regulation via knockdown of reader YTHDF1 in hippocampal neurons alters expression of SME member Apc, and causes synaptic malfunctions manifesting immature spine morphology and dampened excitatory synaptic transmission concomitant with decreased PSD-95 clustering and GluA1 surface expression. Our findings indicate that chemical modifications of synaptic mRNAs critically contribute to synaptic function.

Current Concepts in Pediatric Cervical Spine Trauma

Background: Pediatric spinal trauma is rare and challenging entity. Although cervical spine is commonly affected, it is often missed on routine imaging investigations. Therefore better understanding of growing spine and its patho-physiology is crucial. Methods: Articles related to pediatric cervical trauma were searched on Pubmed and other online research data banks. We have summarized unique anatomy of pediatric spine, investigations followed by common injury patterns, their diagnostic challenges and management. Results: Immature spine follows typical injury patterns, so thorough knowledge of its presentation should be known. Primary physicians should be able to perform initial assessment based on clinical examination and investigations for early diagnosis. High index of suspicion and strategic approach leads to early diagnosis and prevents further morbidity and mortality. Conclusion: Spinal injuries in children are rare and typical. They are often missed and can have fatal consequences. Thorough understanding of pediatric anatomy and injury patterns helps in early diagnosis.