The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats

Pharmacology Research & Perspectives, Journal Year: 2025, Volume and Issue: 13(2)

Published: April 1, 2025

ABSTRACT Anxiety disorder is a persistent, widespread, and intractable mood disorder, the available pharmacotherapies have limited efficacy with significant side effects. Trace amine‐associated receptor 1 (TAAR1) an emerging drug target for neuropsychiatric disorders. This study examined effects underlying mechanisms of novel TAAR1 agonist, PCC0105004, in rat model CUMS‐induced anxiety‐like behavior. The elevated zero maze open field tests test were employed to evaluate anti–anxiety‐like activity PCC0105004. PCC0105004 dose‐dependently attenuated behaviors rats without affecting spontaneous activity. Morphologically, PCC0104005 decreased density dendritic spines amygdala. For mechanistic studies, whole‐genome transcriptomic analysis revealed differences patterns amygdala gene expression anxiety model. These data further confirmed by using RT‐qPCR western blotting, revealing alterations associated genes ( Col1a1, DCN, Ewsr1 ) known regulate synaptic plasticity, was able reverse these changes. results suggest that promising anxiolytic candidate pharmacotherapy warrants examination development.

Language: Английский

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Development of a Non-Derivatized LC-MS/MS Method for Simultaneous Quantification of Ten Neurotransmitters in Five Neuroinflammatory Mouse Models

Talanta Open, Journal Year: 2025, Volume and Issue: unknown, P. 100449 - 100449

Published: April 1, 2025

Language: Английский

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GABAergic neurons in central amygdala contribute to orchestrating anxiety-like behaviors and breathing patterns

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 14, 2025

Language: Английский

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Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression‐Like Behaviors Through Enhanced Synaptic Pruning in Male Mice

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(4)

Published: April 1, 2025

ABSTRACT Aims Microglia, as resident macrophages in the brain, play an important role depression. Heat shock protein 60 (HSP60), a chaperone protein, plays cell stress. However, of microglial HSP60 depression remains unclear. Methods CX3CR1‐CreER was used to generate microglial‐specific knockout (HSP60 cKO) mice. Behavioral tests, western blotting, Golgi staining, biochemical assays, and proteomics were employed assess depression‐like symptoms, activation, synaptic changes. Results cKO male mice exhibited depressive‐like behaviors, without anxiety‐like behavior, including increased immobility forced swimming tail suspension reduced sucrose preference, elevated corticosterone (CORT) levels, indicating HPA axis activation. Microglial activation confirmed by expression levels CD68 CD86, transcription cybb gene, branch complexity. Enhanced phagocytosis excitatory synapses, dendritic spine density, decreased glutamate observed, with downregulation proteins (AMPAR2, Synapsin‐1, PSD95), dysregulated pruning. Moreover, GO analysis showed 20 significant differentially expressed (DEPs) from are associated presynaptic endosome, which crucial maintaining function. Treatment PLX3397, CSF1R inhibitor, alleviated behaviors restored density Conclusions deletion microglia leads overactivation microglia, impaired function, highlighting importance homeostasis mood regulation potential therapeutic modulation.

Language: Английский

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Microglia specific Csf1r haploinsufficiency induces depressive-like behaviors by promoting NLRP6/caspase-1 signaling in mice

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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