The best-laid plans go oft awry: synaptogenic growth factor signaling in neuropsychiatric disease

Growth factors play important roles in synapse formation. Mouse models of neuropsychiatric diseases suggest that defects in synaptogenic growth factors, their receptors, and signaling pathways can lead to disordered neural development and various behavioral phenotypes, including anxiety, memory problems, and social deficits. Genetic association studies in humans have found evidence for similar relationships between growth factor signaling pathways and neuropsychiatric phenotypes. Accumulating data suggest that dysfunction in neuronal circuitry, caused by defects in growth factor-mediated synapse formation, contributes to the susceptibility to multiple neuropsychiatric diseases, including epilepsy, autism, and disorders of thought and mood (e.g., schizophrenia and bipolar disorder, respectively). In this review, we will focus on how specific synaptogenic growth factors and their downstream signaling pathways might be involved in the development of neuropsychiatric diseases

QTL analyses of temporal and intensity components of home-cage activity in KJR and C57BL/6J strains

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BDNF receptor TrkB as the mediator of the antidepressant drug action

Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB has for a long time been recognized as a critical mediator of the antidepressant drug action, but BDNF signaling has been considered to be activated indirectly through the action of typical and rapid-acting antidepressants through monoamine transporters and glutamate NMDA receptors, respectively. However, recent findings demonstrate that both typical and the fast-acting antidepressants directly bind to TrkB and thereby allosterically potentiate BDNF signaling, suggesting that TrkB is the direct target for antidepressant drugs. Increased TrkB signaling particularly in the parvalbumin-expressing interneurons orchestrates iPlasticity, a state of juvenile-like enhanced plasticity in the adult brain. iPlasticity sensitizes neuronal networks to environmental influences, enabling rewiring of networks miswired by adverse experiences. These findings have dramatically changed the position of TrkB in the antidepressant effects and they propose a new end-to-end model of the antidepressant drug action. This model emphasizes the enabling role of antidepressant treatment and the active participation of the patient in the process of recovery from mood disorders.Peer reviewe

Immature-like molecular expression patterns in the hippocampus of a mouse model of dementia with Lewy body-linked mutant β-synuclein

Abstract Aim Maturation abnormalities of the brain cells have been suggested in several neuropsychiatric disorders, including schizophrenia, bipolar disorder, autism spectrum disorders, and epilepsy. In this study, we examined the expression patterns of neuronal maturation markers in the brain of a mouse model of dementia with Lewy body-linked mutant β-synuclein (βS), especially in the hippocampus, to explore whether such brain abnormalities occur in neurodegenerative disorders as well. Methods Quantitative PCR (qPCR) and immunohistochemical analyses were performed using the hippocampus of 14-month-old P123H βS transgenic (Tg) mice to evaluate the expression of molecular markers for maturation of dentate granule cells. Results Based on qPCR results, expression of Tdo2 and Dsp (markers of mature granule cells) was decreased and that of Drd1a (a marker of immature granule cells) was increased in the hippocampus of P123H βS Tg mice compared to that in wild-type controls. Immunohistochemical analysis revealed decreased expression of mature granule cell markers Calb1 and Gria1, along with increased expression of the microglial marker Iba1, in the hippocampal dentate gyrus region of P123H βS Tg mice. P123H βS Tg mice exhibited immature-like neuronal molecular expression patterns and microgliosis in the hippocampus. Pseudo-immaturity of dentate granule cells, associated with neuroinflammation, may be a shared endophenotype in the brains of at least a subgroup of patients with neuropsychiatric disorders and neurodegenerative diseases

The Possibility of Digital Imaging in the Diagnosis of Occlusal Caries

The aim of this study was to assess the possibility of digital image analysis of pit-and-fissure discoloration in order to diagnose caries. Digital images showing pit-and-fissure discoloration in 100 teeth of 19 patients were analyzed to obtain the fractal dimension (FD) and the proportion of the area of pit-and-fissure discoloration to the area of occlusal surface (PA). DIAGNOdent values were measured (DD), and dentists' diagnoses were also obtained. The sensitivity and specificity of FD, PA, DD, and the combination of FD and PA compared to the dentists' diagnoses were calculated. The sensitivities of FD, PA, DD, and the combination of FD and PA were 0.89, 0.47, 0.69, and 0.86, respectively, and the specificities were 0.84, 0.95, 0.91, and 0.86, respectively. Although further research is needed for the practical use, it is possible to use the analysis of digital images of pit-and-fissure molar discoloration as a diagnostic tool

Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66364/1/j.1471-4159.2008.05335.x.pd