Prog Neuropsychopharmacol Biol Psychiatry
January 2025
Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin to alleviate behavioral despair and cognitive deficits in a rodent model of chronic stress, focusing on the interplay between the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Endocannabinoid System (ECS). Twenty-two male Wistar rats were divided into control and stress groups.
View Article and Find Full Text PDFCognitive disorders such as major depressive disorder and bipolar disorder severely compromise brain function and neuronal activity. Treatments to restore cognitive abilities can have severe side effects due to their intense and excitatory nature, in addition to the fact that they are expensive and invasive. Low-field magnetic stimulation (LFMS) is a novel non-invasive proposed treatment for cognitive disorders.
View Article and Find Full Text PDFCajal-Retzius (CR) cells are transient neurons with long-lasting effects on the architecture and circuitry of the neocortex and hippocampus. Contrary to the prevailing assumption that CR cells completely disappear in rodents shortly after birth, a substantial portion of these cells persist in the hippocampus throughout adulthood. The role of these surviving CR cells in the adult hippocampus is largely unknown, partly because of the paucity of suitable tools to dissect their functions in the adult versus the embryonic brain.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
December 2023
The interplay of social, psychological, and biological stresses can trigger mental health conditions such as major depressive disorder (MDD), adjustment disorder, and posttraumatic stress disorder (PTSD). The endocannabinoid system (ECS), comprising endocannabinoids and cannabinoid receptors, is the critical pathway that mediates responses to stress stimuli. This study aimed to investigate the ECS's impact on responding to chronic social instability stress (SIS).
View Article and Find Full Text PDFDepression is a common and disabling comorbidity of multiple sclerosis (MS), with currently no clear guidelines for treatment. Low-field magnetic stimulation (LFMS), a novel non-invasive neuromodulation intervention, has been previously demonstrated to rapidly alleviate mood disorders. The aim of the present study was to investigate the effects of LFMS on depression-like behaviors and demyelination in a well-established mouse model of MS.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2021
The F115C mutation in the MATR3 gene has been linked to amyotrophic lateral sclerosis (ALS). To determine the pathogenicity of the F115C mutation and the mechanism by which this mutation causes ALS, we generated mice that harbor the F115C mutation in the endogenous murine Matr3 locus. Heterozygous or homozygous MATR3 F115C knock-in mice were viable and did not exhibit motor deficits up to 2 years of age.
View Article and Find Full Text PDFA missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system.
View Article and Find Full Text PDFThe replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (Bpgm) gene confers protection against both Plasmodium-induced cerebral malaria and blood-stage malaria.
View Article and Find Full Text PDFMutations in the nuclear matrix protein Matrin 3 (MATR3) have been identified in amyotrophic lateral sclerosis and myopathy. To investigate the mechanisms underlying MATR3 mutations in neuromuscular diseases and efficiently screen for modifiers of MATR3 toxicity, we generated transgenic MATR3 flies. Our findings indicate that expression of wild-type or mutant MATR3 in motor neurons reduces climbing ability and lifespan of flies, while their expression in indirect flight muscles (IFM) results in abnormal wing positioning and muscle degeneration.
View Article and Find Full Text PDFSignificant research efforts are ongoing to elucidate the complex molecular mechanisms underlying amyotrophic lateral sclerosis (ALS), which may in turn pinpoint potential therapeutic targets for treatment. The ALS research field has evolved with recent discoveries of numerous genetic mutations in ALS patients, many of which are in genes encoding RNA binding proteins (RBPs), including TDP-43, FUS, ATXN2, TAF15, EWSR1, hnRNPA1, hnRNPA2/B1, MATR3 and TIA1. Accumulating evidence from studies on these ALS-linked RBPs suggests that dysregulation of RNA metabolism, cytoplasmic mislocalization of RBPs, dysfunction in stress granule dynamics of RBPs and increased propensity of mutant RBPs to aggregate may lead to ALS pathogenesis.
View Article and Find Full Text PDFPyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P.
View Article and Find Full Text PDFInfectious diseases are responsible for over 25% of deaths globally, but many more individuals are exposed to deadly pathogens. The outcome of infection results from a set of diverse factors including pathogen virulence factors, the environment, and the genetic make-up of the host. The completion of the human reference genome sequence in 2004 along with technological advances have tremendously accelerated and renovated the tools to study the genetic etiology of infectious diseases in humans and its best characterized mammalian model, the mouse.
View Article and Find Full Text PDFJ Vet Diagn Invest
January 2012
Seneca Valley virus (SVV), a member of the Picornaviridae family, was implicated in a suspicious vesicular disease discovered in pigs from Canada in 2007. Because any outbreak of vesicular disease in pigs is assumed to be foot-and-mouth disease (FMD) until confirmed otherwise, a test for diagnosing the presence of SVV would be a very useful tool. To develop the diagnostic tests for SVV infection, 5 monoclonal antibodies (mAbs) were produced from mice immunized with binary ethylenimine (BEI)-inactivated SVV.
View Article and Find Full Text PDFPoxviruses are important human and animal pathogens that have evolved elaborate strategies for antagonizing host innate and adaptive immunity. The E3 protein of vaccinia virus, the prototypic member of the orthopoxviruses, functions as an inhibitor of innate immune signaling and is essential for vaccinia virus replication in vivo and in many human cell culture systems. However, the function of orthologues of E3 expressed by poxviruses of other genera with different host specificity remains largely unknown.
View Article and Find Full Text PDFThe vaccinia virus double-stranded RNA binding protein E3 has been demonstrated to inhibit the expression of cytokines, including beta interferon (IFN-beta) and tumor necrosis factor alpha (TNF-alpha). However, few details regarding the molecular mechanisms of this inhibition have been described. Using real-time PCR arrays, we found that E3 suppressed the induction of a diverse array of cytokines representing members of the IFN, interleukin (IL), TNF, and transforming growth factor cytokine families.
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