The Presynaptic Scaffold Protein Bassoon in Forebrain Excitatory Neurons Mediates Hippocampal Circuit Maturation: Potential Involvement of TrkB Signalling

A presynaptic active zone organizer protein Bassoon orchestrates numerous important functions at the presynaptic active zone. We previously showed that the absence of Bassoon exclusively in forebrain glutamatergic presynapses (BsnEmx1cKO) in mice leads to developmental disturbances in dentate gyrus (DG) affecting synaptic excitability, morphology, neurogenesis and related behaviour during adulthood. Here, we demonstrate that hyperexcitability of the medial perforant path-to-DG (MPP-DG) pathway in BsnEmx1cKO mice emerges during adolescence and is sustained during adulthood. We further provide evidence for a potential involvement of tropomyosin-related kinase B (TrkB), the high-affinity receptor for brain-derived neurotrophic factor (BDNF), mediated signalling. We detect elevated TrkB protein levels in the dorsal DG of adult mice (~3–5 months-old) but not in adolescent (~4–5 weeks-old) mice. Electrophysiological analysis reveals increased field-excitatory-postsynaptic-potentials (fEPSPs) in the DG of the adult, but not in adolescent BsnEmx1cKO mice. In line with an increased TrkB expression during adulthood in BsnEmx1cKO, blockade of TrkB normalizes the increased synaptic excitability in the DG during adulthood, while no such effect was observed in adolescence. Accordingly, neurogenesis, which has previously been found to be increased in adult BsnEmx1cKO mice, was unaffected at adolescent age. Our results suggest that Bassoon plays a crucial role in the TrkB-dependent postnatal maturation of the hippocampus.

Management of developmental disturbances in a 12 year-old child- A multidisciplinary approach

Manifestation of developmental disturbances of the teeth can be in the form of variations in number, position, size, shape, eruption or structure. Such disturbances may be independent or associated with more generalised disorders. The form and structure of the teeth may be affected by local and general factors. This paper is a report of a 12-year-old girl with missing both permanent mandibular central incisors along with permanent maxillary right central incisor. Past history revealed trauma 5 years back due to fall from height. Radiographic examination revealed congenitally missing permanent mandibular left and right central incisors and dilacerated permanent maxillary right central incisor. A multidisciplinary approach has been presented for management of such cases.

GENETICS: A MODIFICATION IN DENTISTRY

Genetics is a branch of biology which can be dened as the study of genes and heredity. Genetics when seen in relation to oral health can show various manifestations ranging from developmental disturbances to precancerous and cancerous lesions. Signicant advances in research methods and newly emerging partnerships between private and public sector interests are creating new possibilities for utilization of genetic information for the diagnosis and treatment of human diseases. The availability and application of genetic information to the understanding of normal and abnormal human growth and development are fundamentally changing the way we approach the study of human diseases. As a result, the issues and principles of medical genetics are coming to bear across all disciplines of health care. In this review, we discuss some of the potential applications of human molecular genetics for the diagnosis and treatment of oral diseases. This discussion is presented in the context of the ongoing technological advances and conceptual changes that are occurring in the eld of medical genetics.

The Applicability and Performance of Tools Used to Assess the Father-Offspring Relationship in Relation to Parental Psychopathology and Offspring Outcomes

Introduction: Father-infant interactions are important for optimal offspring outcomes. Moreover, paternal perinatal psychopathology is associated with psychological and developmental disturbances in the offspring, and this risk may increase when both parents are unwell. While, the father-offspring relationship is a plausible mechanism of risk transmission, there is presently no “gold standard” tool for assessing the father-offspring relationship. Therefore, we systematically searched and reviewed the application and performance of tools used to assess the father-offspring relationship from pregnancy to 24-months postnatal.Methods: Four electronic databases (including MEDLINE, PsycINFO, Maternity and Infant Care Database, and CINAHL) were searched. Selected articles included evidence of father-offspring relationship assessment in relation to parental perinatal psychopathology and/or offspring outcomes. Data was extracted and synthesized according to the following: (i) evidence supporting the performance of tools in terms of their psychometric properties when applied in the context of fathers, (ii) tool specific characteristics, and (iii) study specific methodological aspects in which the tool was embedded.Results: Of the 30,500 records eligible for screening, 38 unique tools used to assess the father-offspring relationship were identified, from 61 studies. Ten tools were employed in the context of paternal psychopathology, three in the context of maternal psychopathology, and seven in the context of both maternal and paternal psychopathology, while nine tools were applied in the context of offspring outcomes only. The remaining nine tools were used in the context of both parental psychopathology (i.e., paternal, and/or maternal psychopathology) and offspring outcomes. Evidence supporting the psychometric robustness of the extracted observational, self-report and interview-based tools was generally limited. Most tools were originally developed in maternal samples—with few tools demonstrating evidence of content validation specific to fathers. Furthermore, various elements influencing tool performance were recognized—including variation in tool characteristics (e.g., relationship dimensions assessed, assessment mode, and scoring formats) and study specific methodological aspects, (e.g., setting and study design, sample characteristics, timing and nature of parental psychopathology, and offspring outcomes).Conclusion: Given the strengths and limitations of each mode of assessment, future studies may benefit from a multimethod approach to assessing the father-offspring relationship, which may provide a more accurate assessment than one method alone.

Regenerative Therapies to Restore Interneuron Disturbances in Experimental Models of Encephalopathy of Prematurity

Encephalopathy of Prematurity (EoP) is a major cause of morbidity in (extreme) preterm neonates. Though the majority of EoP research has focused on failure of oligodendrocyte maturation as an underlying pathophysiological mechanism, recent pioneer work has identified developmental disturbances in inhibitory interneurons to contribute to EoP. Here we investigated interneuron abnormalities in two experimental models of EoP and explored the potential of two promising treatment strategies, namely intranasal mesenchymal stem cells (MSCs) or insulin-like growth factor I (IGF1), to restore interneuron development. In rats, fetal inflammation and postnatal hypoxia led to a transient increase in total cortical interneuron numbers, with a layer-specific deficit in parvalbumin (PV)+ interneurons. Additionally, a transient excess of total cortical cell density was observed, including excitatory neuron numbers. In the hippocampal cornu ammonis (CA) 1 region, long-term deficits in total interneuron numbers and PV+ subtype were observed. In mice subjected to postnatal hypoxia/ischemia and systemic inflammation, total numbers of cortical interneurons remained unaffected; however, subtype analysis revealed a global, transient reduction in PV+ cells and a long-lasting layer-specific increase in vasoactive intestinal polypeptide (VIP)+ cells. In the dentate gyrus, a long-lasting deficit of somatostatin (SST)+ cells was observed. Both intranasal MSC and IGF1 therapy restored the majority of interneuron abnormalities in EoP mice. In line with the histological findings, EoP mice displayed impaired social behavior, which was partly restored by the therapies. In conclusion, induction of experimental EoP is associated with model-specific disturbances in interneuron development. In addition, intranasal MSCs and IGF1 are promising therapeutic strategies to aid interneuron development after EoP.

Dens evaginatus and dens invaginatus: A report of two cases

Introduction: Developmental disturbances of teeth at the stage of morpho-differentiation have been related to abnormalities associated with changes in the tooth shape and size. Dens evaginatus and dens invaginatus are the developmental variations of the human dentition. Dens evaginatus, a rare anomaly characterized by the presence of a tubercle on the occlusal surface of teeth is seen to occur due to abnormal proliferation and folding of the inner enamel epithelium and part of the dental papilla into the stellate reticulum of the enamel organ; whereas, dens invaginatus is seen to occur due to infolding of the enamel and dentine into the pulp cavity and sometimes extending to the root apex. Case report: We report cases with bilateral dens evaginatus in mandibular second premolars and dens invaginatus in maxillary lateral incisor. Conclusion: Such developmental anomalies of teeth deserve clinical importance, as high chances of early pulpal pathosis.

Acetylcholine and Its Receptors in Honeybees: Involvement in Development and Impairments by Neonicotinoids

Acetylcholine (ACh) is the major excitatory neurotransmitter in the insect central nervous system (CNS). However, besides the neuronal expression of ACh receptors (AChR), the existence of non-neuronal AChR in honeybees is plausible. The cholinergic system is a popular target of insecticides because the pharmacology of insect nicotinic acetylcholine receptors (nAChRs) differs substantially from their vertebrate counterparts. Neonicotinoids are agonists of the nAChR and are largely used in crop protection. In contrast to their relatively high safety for humans and livestock, neonicotinoids pose a threat to pollinating insects such as bees. In addition to its effects on behavior, it becomes increasingly evident that neonicotinoids affect developmental processes in bees that appear to be independent of neuronal AChRs. Brood food (royal jelly, worker jelly, or drone jelly) produced in the hypopharyngeal glands of nurse bees contains millimolar concentrations of ACh, which is required for proper larval development. Neonicotinoids reduce the secreted ACh-content in brood food, reduce hypopharyngeal gland size, and lead to developmental impairments within the colony. We assume that potential hazards of neonicotinoids on pollinating bees occur neuronally causing behavioral impairments on adult individuals, and non-neuronally causing developmental disturbances as well as destroying gland functioning.