Expression and dendritic trafficking of BDNF-6 splice variant are impaired in knock-in mice carrying human BDNF Val66Met polymorphism

BACKGROUND: The human Val66Met polymorphism in brain-derived neurotrophic factor (BDNF), a key factor in neuroplasticity, synaptic function, and cognition, has been implicated in the pathophysiology of neuropsychiatric and neurodegenerative disorders. BDNF is encoded by multiple transcripts with distinct regulation and localization, but the impact of the Val66Met polymorphism on BDNF regulation remains unclear. METHODS: In BDNF Val66Met knock-in mice, which recapitulate the phenotypic hallmarks of individuals carrying the BDNF(Met) allele, we measured expression levels, epigenetic changes at promoters, and dendritic trafficking of distinct BDNF transcripts using quantitative PCR, chromatin immunoprecipitation (ChIP), and in situ hybridization. RESULTS: BDNF-4 and BDNF-6 transcripts were reduced in BDNF(Met/Met) mice, compared with BDNF(Val/Val) mice. ChIP for acetyl-histone H3, a marker of active gene transcription, and trimethyl-histone-H3-Lys27 (H3K27me3), a marker of gene repression, showed higher H3K27me3 binding to exon 5, 6, and 8 promoters in BDNF(Met/Met). The H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) is involved in epigenetic regulation of BDNF expression, because in neuroblastoma cells BDNF expression was increased both by short interference RNA for EZH2 and incubation with 3-deazaneplanocin A, an inhibitor of EZH2. In situ hybridization for BDNF-2, BDNF-4, and BDNF-6 after pilocarpine treatment showed that BDNF-6 transcript was virtually absent from distal dendrites of the CA1 and CA3 regions in BDNF(Met/Met) mice, while no changes were found for BDNF-2 and BDNF-4. CONCLUSIONS: Impaired BDNF expression and dendritic targeting in BDNF(Met/Met) mice may contribute to reduced regulated secretion of BDNF at synapses, and may be a specific correlate of pathology in individuals carrying the Met allele

Enteroviruses in Blood Diabetes and Viruses

Viruses in diabetes - findings in human

Multiple synchronous rhabdomyomas in the tongue and floor of the mouth: case report

Observation: A 61-year-old male patient presented with tongue and base floor of the mouth firm swelling with intact overlying mucosa with ballottement by bimanual palpation. Histopathological examination and immunodiagnosis revealed this mass as adult rhabdomyoma. Comments: Any tongue base or floor of the mouth mass with intact overlying mucosa should be approached by magnetic resonance imaging with great concern of rhabdomyoma

Enteroviruses and causality of type 1 diabetes: how close we are?

Organ-specific autoimmunity frequently affects the endocrine system, including pancreatic islets. Type 1 diabetes mellitus (T1D) derives from the autoimmune destruction of insulin-secreting \u3b2-cells that is triggered by environmental factors (1, 2). Genetic predisposition accounts for 36\u201350% of disease susceptibility as demonstrated in monozygotic twin studies (3\u20135). Approximately 90% of new cases lack a family history of T1D indicating a large contribution of exogenous factors to pathogenesis. A variety of associations with viral infections have been reported for human diabetes including rubella, mumps, and cytomegalovirus. However, among investigated agents, human enteroviruses (HEVs) appear to play a prominent role (1)

Mandibular coronoid process grafting for alveolar ridge defects

Objective. We describe the clinical results of mandibular augmentation with coronoid process bone grafts for dental implant insertion. Study Design. Fifteen patients with vertical and transverse defects of the posterior alveolar process of the mandible were treated. All patients underwent mandibular rehabilitation with autogenous coronoid process bone grafts via minimal-access surgery. After 6 months, 40 dental implants were inserted. Results. At the time of implant insertion, the grafted alveolar ridges showed mean transverse and vertical augmentations of 3.07 and 2.80 mm, respectively. At 24 months after implant surgery, the cumulative implant survival rate was 95% and mean marginal bone loss was 1.6 ± 0.18 mm. No complete bone graft loss or infection occurred. Conclusions. Coronoid process bone grafts can be used to reconstruct moderate defects in edentulous alveolar processes. The insertion of the graft with minimal access in a tunneled fashion minimizes the risk of infection.</br