A sexually dimorphic signature of activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the prefrontal cortex.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. We and others hypothesize that diminished activity-dependent neural signaling is a common molecular pathway dysregulated in ASD caused by diverse genetic mutations. Brain-derived neurotrophic factor (BDNF) is a key growth factor mediating activity-dependent neural signaling in the brain.

Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats.

Cancer patients undergoing chemotherapy often experience anorexia and weight loss that substantially deteriorates overall health, reduces treatment tolerance and quality of life, and worsens oncologic outcomes. There are currently few effective therapeutic options to mitigate these side effects. The central melanocortin system, which plays a pivotal role in regulating appetite and energy homeostasis, presents a logical target for treating anorexia and weight loss.

Aging alters the expression of trophic factors and tight junction proteins in the mouse choroid plexus.

Background: The choroid plexus (CP) is an understudied tissue in the central nervous system and is primarily implicated in cerebrospinal fluid (CSF) production. CP also produces numerous neurotrophic factors (NTF) which circulate to different brain regions. Regulation of NTFs in the CP during natural aging is largely unknown.

Lipid Nanoparticles Elicit Reactogenicity and Sickness Behavior in Mice Via Toll-Like Receptor 4 and Myeloid Differentiation Protein 88 Axis.

mRNA therapeutics encapsulated in lipid nanoparticles (LNPs) offer promising avenues for treating various diseases. While mRNA vaccines anticipate immunogenicity, the associated reactogenicity of mRNA-loaded LNPs poses significant challenges, especially in protein replacement therapies requiring multiple administrations, leading to adverse effects and suboptimal therapeutic outcomes. Historically, research has primarily focused on the reactogenicity of mRNA cargo, leaving the role of LNPs understudied in this context.

Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress.

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI].

Regulation of trophic factors in the choroid plexus of aged mice.

Background: The choroid plexus (CP) is an understudied tissue in the central nervous system (CNS), primarily implicated in cerebrospinal fluid (CSF) production. Additionally, CP produces numerous neurotrophic factors (NTF), which circulate to different regions of the brain. Regulation of NTF in the CP during natural aging has yet to be discovered.

Synergism of Carbamoylated Erythropoietin and Insulin-like Growth Factor-1 in Immediate Early Gene Expression.

Trophic factors are secreted proteins that can modulate neuronal integrity, structure, and function. Previous preclinical studies have shown synergistic effects on decreasing apoptosis and improving behavioral performance after stroke when combining two such trophic factors, erythropoietin (EPO) and insulin-like growth factor-1 (IGF-1). However, EPO can elevate the hematocrit level, which can be life-threatening for non-anemic individuals.

Carbamoylated Erythropoietin-Induced Cerebral Blood Perfusion and Vascular Gene Regulation.

Cerebral hypoperfusion is associated with enhanced cognitive decline and increased risk of neuropsychiatric disorders. Erythropoietin (EPO) is a neurotrophic factor known to improve cognitive function in preclinical and clinical studies of neurodegenerative and psychiatric disorders. However, the clinical application of EPO is limited due to its erythropoietic activity that can adversely elevate hematocrit in non-anemic populations.

Diminished activity-dependent BDNF signaling differentially causes autism-like behavioral deficits in male and female mice.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. Recent human genetic studies have identified multiple high-risk genes for ASD, which produce similar phenotypes, indicating that diverse genetic factors converge to common molecular pathways. We and others have hypothesized that activity-dependent neural signaling is a convergent molecular pathway dysregulated in ASD.

Antidepressant-like effects of trophic factor receptor signaling.

A significant body of research has demonstrated that antidepressants regulate neurotrophic factors and that neurotrophins themselves are capable of independently producing antidepressant-like effects. While brain derived neurotrophic factor (BDNF) remains the best studied molecule in this context, there are several structurally diverse trophic factors that have shown comparable behavioral effects, including basic fibroblast growth factor (FGF-2), insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF). In this review we discuss the structural and biochemical signaling aspects of these neurotrophic factors with antidepressant activity.

Evaluation of a protein-to-creatinine dipstick diagnostic test for proteinuria screening in selected antenatal care clinics in three Districts in the Bono-East Region of Ghana.

Background: Preeclampsia and eclampsia contribute significantly to maternal and newborn deaths worldwide. Early and accurate identification of pregnant women at risk can avert these deaths, but the necessary diagnostics are not widely available. A protein and creatinine ratio, rather than a measurement of protein alone, may provide better identification of proteinuria.

Erythropoietin and Non-Erythropoietic Derivatives in Cognition.

Cognitive deficits are widespread in psychiatric disorders, including major depression and schizophrenia. These deficits are known to contribute significantly to the accompanying functional impairment. Progress in the development of targeted treatments of cognitive deficits has been limited and there exists a major unmet need to develop more efficacious treatments.

A Comparative Analysis of Erythropoietin and Carbamoylated Erythropoietin Proteome Profiles.

In recent years, erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive-enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity and produce adverse effects in non-anemic populations.

Stress and Its Impact on the Transcriptome.

Exposure to stress during the course of a lifetime is inevitable in the animal kingdom. It is the response to stress, the valence of the exposure, and the developmental time point that largely determine the consequences to the initial and subsequent exposures. The versatility of transcriptomic methods to yield rich, high-resolution, information-laden datasets from entire brain regions to single cells makes it a powerful approach to investigate the effects of stress from several angles.

Design and Development of a Behaviorally Active Recombinant Neurotrophic Factor.

Introduction: Carbamoylated erythropoietin (CEPO) is a chemically engineered, nonhematopoietic derivative of erythropoietin (EPO) that retains its antidepressant and pro-cognitive effects, which are attributed to the increased expression of neurotrophic factors like brain derived neurotrophic factor (BDNF), in the central nervous system. However, the chemical modification process which produces CEPO from erythropoietin (EPO) requires pure EPO as raw material, is challenging to scale-up and can also cause batch-to-batch variability. To address these key limitations while retaining its behavioral effects, we designed, expressed and analyzed a triple, glutamine, substitution recombinant mimetic of CEPO, named QPO.

Cerebrospinal fluid proteome evaluation in major depressive disorder by mass spectrometry.

Background: Depression affects approximately 7.1% of the United States population every year and has an annual economic burden of over $210 billion dollars. Several recent studies have sought to investigate the pathophysiology of depression utilizing focused cerebrospinal fluid (CSF) and serum analysis.

Alpha-gal Allergy in a 6-Year-Old Male: A Case Report.

Alpha-gal allergy is a reaction where the immunoglobulin E antibody elicits a response to galactosealpha-1,3-galactose (alpha-gal) which is a mammalian oligosaccharide epitope found in nonprimate mammalian. After being exposed to a tick bite, particularly the Lone Star tick (Amblyomma americanum), an individual has been known to develop an alpha-gal allergy. Our patient presented with symptoms of delayed-onset allergy 3-8 hours after consuming mammalian meat products including beef and pork.

Effect of a theory-based hand hygiene educational intervention for enhancing behavioural outcomes in Ghanaian schools: a cluster-randomised controlled trial.

Objectives: The study sought to determine whether a hand hygiene educational intervention underpinned by educational and psychosocial theories is effective in enhancing behavioural intention and proper handwashing practices among school children.

Methods: The study was a cluster-randomised controlled trial, with schools constituting the clusters. At baseline, 717 pupils organised in four clusters were recruited.

Injury rate and risk factors among small-scale gold miners in Ghana.

Background: To determine the potential risk factors for injury, estimate the annual injury rate and examine the safety perceptions, and use of personal protective equipment among small-scale gold miners in Ghana.

Methods: A cross-sectional survey was carried out with 494 small-scale gold miners from four major mining districts in Ghana. A household-based approach was used to obtain a representative sample of miners.

Effects of restraint stress on the regulation of hippocampal glutamate receptor and inflammation genes in female C57BL/6 and BALB/c mice.

The two strains of inbred mice, BALB/c and C57BL/6, are widely used in pre-clinical psychiatry research due to their differences in stress susceptibility. Gene profiling studies in these strains have implicated the inflammation pathway as the main contributor to these differences. We focused our attention on female mice and tested their response to 5- or 10-day exposure to restraint stress.

Occupational injury burden among gold miners in Ghana.

The mining environment is particularly dangerous in low- and middle-income countries. We sought to better understand the burden, characteristics and risk factors associated with gold mining, through a household survey of 1,029 miners in four districts, in Ghana. We found a high burden of injuries, with 25.

Computational analysis of ligand-receptor interactions in wild-type and mutant erythropoietin complexes.

Background: Erythropoietin (EPO), a pleiotropic cytokine, binds to its receptor (EPOR) in bone marrow, activating a signaling cascade that results in red blood cell proliferation. A recently discovered naturally occurring EPO mutation (R150Q) at active site 1 (AS1) of the protein was shown to attenuate its canonical downstream signaling, eliminating its hematopoietic effects and causing a fatal anemia. The purpose of this work was to analyze the EPO-EPOR complex computationally to provide a structural explanation for this signaling change.

Orexin 2 receptor stimulation enhances resilience, while orexin 2 inhibition promotes susceptibility, to social stress, anxiety and depression.

Knockdown of orexin/hypocretin 2 receptor (Orx) in the basolateral amygdala (BLA) affects anxious and depressive behavior. We use a new behavioral paradigm, the Stress Alternatives Model (SAM), designed to improve translational impact. The SAM induces social stress in adult male mice by aggression from larger mice, allowing for adaptive decision-making regarding escape.