The linkage-testing strain of ABP/Le mice carries six mutations which express in easily identifiable phenotypes. By crossing this strain with a traditional inbred strain (C57BL/6ByJ) which is the 'wild type' for the mutated ABP/Le loci, we produced Mendelian populations, intercrosses and backcrosses so as to estimate whether the sensitivity to methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine receptor inverse agonist, and anxiety-related behaviour could be related to a common genetically determined substrate. We have shown that one locus on chromosome 9 is associated with beta-CCM-induced seizures and three loci on chromosomes 4, 7 and 9 are associated with anxiogenic processes. Analysis of [3H]flumazenil binding suggested a possible involvement of a Bmax decrease in both beta-CCM-induced seizures and anxiogenic processes. The putative common genetic regulation of both mechanisms is discussed.
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http://dx.doi.org/10.1016/s0928-4257(99)80162-4 | DOI Listing |
Open Biol
January 2025
Department of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Retrotransposon Gag-like (RTL) 8A, 8B and 8C are eutherian-specific genes derived from a certain retrovirus. They cluster as a triplet of genes on the X chromosome, but their function remains unknown. Here, we demonstrate that and play important roles in the brain: their double knockout (DKO) mice not only exhibit reduced social responses and increased apathy-like behaviour, but also become obese from young adulthood, similar to patients with late Prader-Willi syndrome (PWS), a neurodevelopmental genomic imprinting disorder.
View Article and Find Full Text PDFEur J Med Chem
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, Xicheng district, Beijing, 100050, China. Electronic address:
A novel class of 7-phenyl-[1,2,4]triazol-5(4H)-one derivatives was designed and synthesized, and their in vivo anticonvulsant activities were evaluated using subcutaneous pentylenetetrazole (Sc-PTZ) and maximal electroshock (MES) tests. Compounds 3u, 4f and 4k exhibited significant anticonvulsant activities in the Sc-PTZ model with ED values of 23.7, 17.
View Article and Find Full Text PDFHandb Clin Neurol
January 2025
Department of Surgical Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy; Department of Neuroscience, Psychology Unit, University of Pisa Azienda Ospedaliera Universitaria Pisana (AUOP), Pisa, Italy.
Insomnia disorder is a frequent sleep disorder leading to significant health and economic consequences. It has been proposed that individuals with insomnia may experience compromised deactivation systems of arousal, leading to a chronic state of hyperactivation of arousal known as hyperarousal, along with instability in the flip-flop system. Such disruptions may have a primarily impact on the sleep homeostatic drive process.
View Article and Find Full Text PDFPharmacol Ther
January 2025
Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:
While benzodiazepines have been a mainstay of the pharmacotherapy of anxiety disorders, their short-term efficacy and risk of abuse have driven the exploration of alternative treatment approaches. The endocannabinoid (eCB) system has emerged as a key modulator of anxiety-related processes, with evidence suggesting dynamic interactions between the eCB system and the GABAergic system, the primary target of benzodiazepines. According to the existing literature, the activation of the cannabinoid receptors has been shown to exert anxiolytic effects, while their blockade or genetic deletion results in heightened anxiety-like responses.
View Article and Find Full Text PDFNeuromolecular Med
January 2025
Biochemistry and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.
Hypoxia is a significant stressor, and stabilized hypoxia-inducible factor-1α (HIF-1α) regulates the expression of numerous genes, leading to various biochemical, molecular, physiological and genomic changes. The body's oxygen-sensing system activates gene expression to protect brain tissues from hypoxia. Gamma-aminobutyric acid, an inhibitory neurotransmitter, regulates brain excitability during hypoxia through the activation of HIF-1 α.
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