Untreated behavioral health conditions among the perinatal population are associated with high mortality and morbidity. We examined trends of behavioral health conditions and treatment received by perinatal Medicaid beneficiaries and described the characteristics of providers treat-ing these beneficiaries from 2017 to 2022. Results indicated that 24.
View Article and Find Full Text PDFJ Neurodev Disord
October 2020
Background: Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, "higher" sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex.
View Article and Find Full Text PDFJ Hand Ther
October 2021
Study Design: Case series.
Introduction: Pain and injury at the radial and ulnar aspects of the wrist due to overuse or trauma are commonly treated in hand therapy clinics.
Purpose Of Study: Describe two orthoses that allow targeted rest and recovery of involved anatomical structure(s) while preserving function of surrounding uninvolved structures in patients who have sustained overuse or traumatic injury at the radial or ulnar aspect of the wrist.
Mol Cell Neurosci
July 2019
EPAC2 is a guanine nucleotide exchange factor that regulates GTPase activity of the small GTPase Rap and Ras and is highly enriched at synapses. Activation of EPAC2 has been shown to induce dendritic spine shrinkage and increase spine motility, effects that are necessary for synaptic plasticity. These morphological effects are dysregulated by rare mutations of Epac2 associated with autism spectrum disorders.
View Article and Find Full Text PDFDendritic spine morphology and dendritic arborization are key determinants of neuronal connectivity and play critical roles in learning, memory and behavior function. Recently, defects of ZBTB20, a BTB and zinc finger domain containing transcriptional repressor, have been implicated in a wide range of neurodevelopmental disorders, including intellectual disability and autism. Here we show distinct effects of expression of two major isoforms, long and short, of ZBTB20, and its neurodevelopmental disorder-linked variants, on dendritic architecture of cultured rat cortical pyramidal neurons.
View Article and Find Full Text PDFBackground: The induction of beige adipocytes in s.c. white adipose tissue (WAT) depots of humans is postulated to improve glucose and lipid metabolism in obesity.
View Article and Find Full Text PDFAppropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded by within the ASD risk locus 5p14.
View Article and Find Full Text PDFMutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein.
View Article and Find Full Text PDFUnlabelled: Individuals with Angelman syndrome (AS) suffer sleep disturbances that severely impair quality of life. Whether these disturbances arise from sleep or circadian clock dysfunction is currently unknown. Here, we explored the mechanistic basis for these sleep disorders in a mouse model of Angelman syndrome (Ube3a(m-/p+) mice).
View Article and Find Full Text PDFPyramidal neurons in the mammalian forebrain receive their synaptic inputs through their dendritic trees, and dendritic spines are the sites of most excitatory synapses. Dendritic spine structure is important for brain development and plasticity. Kalirin-7 is a guanine nucleotide-exchange factor for the small GTPase Rac1 and is a critical regulator of dendritic spine remodeling.
View Article and Find Full Text PDFThe ability of a neuron to transduce extracellular signals into long lasting changes in neuronal morphology is central to its normal function. Increasing evidence shows that coordinated regulation of synaptic and nuclear signaling in response to NMDA receptor activation is crucial for long term memory, synaptic tagging, and epigenetic signaling. Although mechanisms have been proposed for synapse-to-nuclear communication, it is unclear how signaling is coordinated at both subcompartments.
View Article and Find Full Text PDFObjectives: We evaluated whether pancreatic main duct fluid can provide protein biomarkers with prognostic value.
Methods: Mass spectrometry proteomics was applied to as little as 20µL of fluid collected at the time of tumor surgical resection. Biomarker proteins identified for 27 patients were correlated with clinical outcomes.
Plasma proteomic experiments performed rapidly and economically using several of the latest high-resolution mass spectrometers were compared. Four quantitative hyperfractionated plasma proteomics experiments were analyzed in replicates by two AB SCIEX TripleTOF 5600 and three Thermo Scientific Orbitrap (Elite/LTQ-Orbitrap Velos/Q Exactive) instruments. Each experiment compared two iTRAQ isobaric-labeled immunodepleted plasma proteomes, provided as 30 labeled peptide fractions, and 480 LC-MS/MS runs delivered >250 GB of data in 2 months.
View Article and Find Full Text PDFThe biological functions of the neuregulin 1 (NRG1) and ERBB4 genes have received much recent attention due to several studies showing associations between these genes and schizophrenia. Moreover, reduced forebrain dendritic spine density is a consistent feature of schizophrenia. It is thus important to understand the mechanisms whereby NRG1 and erbB4 modulate spine morphogenesis.
View Article and Find Full Text PDFImmunodepletion of abundant plasma proteins increases the depth of proteome penetration by mass spectrometry. However, the nature and extent of immunodepletion and the effect of off-target depletion on the quantitative comparison of the residual proteins have not been critically addressed. We performed mass spectrometry label-free quantitation to determine which proteins were immunodepleted and by how much.
View Article and Find Full Text PDFJ Biol Chem
October 2012
The dendritic field of a neuron, which is determined by both dendritic architecture and synaptic strength, defines the synaptic input of a cell. Once established, a neuron's dendritic field is thought to remain relatively stable throughout a cell's lifetime. Perturbations in a dendritic structure or excitatory tone of a cell and thus its dendritic field are cellular alterations thought to be correlated with a number of psychiatric disorders.
View Article and Find Full Text PDFDeficits in social and communication behaviors are common features of a number of neurodevelopmental disorders. However, the molecular and cellular substrates of these higher order brain functions are not well understood. Here we report that specific alterations in social and communication behaviors in mice occur as a result of loss of the EPAC2 gene, which encodes a protein kinase A-independent cAMP target.
View Article and Find Full Text PDFThe architecture of dendritic arbors determines circuit connectivity, receptive fields, and computational properties of neurons, and dendritic structure is impaired in several psychiatric disorders. While apical and basal dendritic compartments of pyramidal neurons are functionally specialized and differentially regulated, little is known about mechanisms that selectively maintain basal dendrites. Here we identified a role for the Ras/Epac2 pathway in maintaining basal dendrite complexity of cortical neurons.
View Article and Find Full Text PDFObjective: To assess the relationship between possible exposure to smoke from documented open-air burn pits and newly reported lupus and rheumatoid arthritis among Millennium Cohort participants who have deployed in support of operations in Iraq and Afghanistan.
Methods: Prospectively assessed self-reported lupus and rheumatoid arthritis among deployers who completed both 2004-2006 and 2007-2008 questionnaires.
Results: After exclusions, more than 18,000 participants were deployed, including more than 3000 participants deployed within a 3-mile radius of a documented burn pit.
J Occup Environ Med
May 2012
Objective: To investigate the association between US Navy individual augmentee (IA) deployers, who may lack the protective effects of unit cohesion and social support, and newly reported mental health.
Methods: Responses from the Millennium Cohort Study questionnaires were examined for 2086 Navy deployers in this prospective exploratory study. Multivariable logistic regression was used to evaluate IA deployment and newly reported mental health symptoms.
It has been hypothesized that those who entered military service in the pre-September 11, 2001 era might have expectations incongruent with their subsequent experiences, increasing the risk for posttraumatic stress disorder (PTSD) or other mental disorders. A subset of Millennium Cohort Study participants who joined the military during 1995-1999 was selected and compared with a subset of members who joined the military in 2002 or later. Outcomes included new-onset symptoms of PTSD, depression, panic/anxiety, and alcohol-related problems.
View Article and Find Full Text PDFThe objective of this study was to prospectively assess the association between deployment in support of the operations in Iraq and Afghanistan and newly reported lupus and rheumatoid arthritis while also considering the effects of demographic, behavioral, and occupational characteristics. A total of 77,047 (2001-2003) and 31,110 (2004-2006) participants completed the baseline Millennium Cohort questionnaire and were resurveyed approximately every 3 years. Longitudinal analyses were used to assess the adjusted association between deployment to Iraq and Afghanistan with and without combat exposures and newly reported disease.
View Article and Find Full Text PDFSubstantial progress has been made toward understanding the genetic architecture, cellular substrates, brain circuits and endophenotypic profiles of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia and Alzheimer's disease. Recent evidence implicates spiny synapses as important substrates of pathogenesis in these disorders. Although synaptic perturbations are not the only alterations relevant for these diseases, understanding the molecular underpinnings of spine pathology may provide insight into their etiologies and may reveal new drug targets.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2009
The 5-HT(2A) serotonin receptor is the most abundant serotonin receptor subtype in the cortex and is predominantly expressed in pyramidal neurons. The 5-HT(2A) receptor is a target of several hallucinogens, antipsychotics, anxiolytics, and antidepressants, and it has been associated with several psychiatric disorders, conditions that are also associated with aberrations in dendritic spine morphogenesis. However, the role of 5-HT(2A) receptors in regulating dendritic spine morphogenesis in cortical neurons is unknown.
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