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Exploring the molecular mechanisms underlying DSIPs effects, which could pave the way for the development of optimized analogs or targeted therapies

ACTH adrenocorticotropic hormone AD Alzheimer's disease ALLO allopregnanolone AMPA -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ANT adenine nucleotide transporter protein BBB blood-brain barrier BNST bed nucleus of the stria terminalis CB1 cannabinoid receptor 1 CICR Ca 2+ -induced Ca 2+ release CNS central nervous system DA dopamine DAT dopamine transporter DAT KO dopamine transporter knockout DHEA dehydroepiandrosterone DHEAS dehydroepiandrosterone sulfate GABA gamma-aminobutyric acid GAD generalized anxiety disorder GLIC Gloeobacter ligand-gated ion channels GnRH gonadotrophin-releasing hormone HPA axis hypothalamic-pituitary-adrenal axis HRSA Hamilton Rating Scale for Anxiety IL-6 interleukin-6 L-Type VGCC L-type voltage-gated Ca 2+ channel LTD long-term depression LTP long-term potentiation MCI mild cognitive impairment NMDA N-methyl-D-aspartate OATPs organic anion transporting peptides ORAI1 Ca 2+ release-activated Ca 2+ channel protein 1 PAHS pregnanolone hemisuccinate pCREB phosphorylated CREB PET positron emission tomography PCOS polycystic ovary syndrome PREG pregnenolone PregS pregnenolone sulfate PTSD post-traumatic stress disorder PV parvalbumin PXR pregnane xenobiotic receptor P450 scc cytochrome P450 side chain cleavage sEPSC spontaneous excitatory post-synaptic currents 5-HT serotonin SSRIs selective serotonin reuptake inhibitors StAR protein steroidogenic acute regulatory protein STIM1 stromal interaction molecule 1 THDOC tetrahydrodeoxycorticosterone TRH thyrotropin-releasing hormone TRP channels transient receptor potential channels TSPO translocator protein VDAC voltage-dependent anion channel

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Beyond these headline outcomes, studies also report improvements in blood pressure, cholesterol, and insulin sensitivity, painting a picture of a therapy that supports the bodys entire metabolic system

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