Synergistic Roles of Neuropeptide S and Environmental Enrichment in Preclinical Huntington’s Disease Depression Models
CNS Neurol Disord Drug Targets. 2026 Mar 12. doi: 10.2174/0118715273411285251206061525. Online ahead of print.
ABSTRACT
INTRODUCTION: Huntington’s disease (HD) is a progressive neurodegenerative disorder marked by motor, cognitive, and psychiatric impairments, with depression as a major comorbidity. Existing treatments for Huntington-related depression are inadequate, highlighting the need for strategies that target molecular mechanisms underlying mood dysregulation.
METHOD: This review examines the mechanistic interplay between environmental enrichment (EE), a paradigm enhancing sensory, cognitive, and social stimulation and Neuropeptide S (NPS), a neuropeptide involved in stress modulation and emotional regulation. It focuses on their potential synergistic effects in modulating depression-associated molecular pathways in HD.
RESULTS: EE activates signalling cascades that promote synaptic plasticity and neurogenesis, including the upregulation of brain-derived neurotrophic factor (BDNF), enhanced activation of cAMP response element-binding protein (CREB), and remodelling of glutamatergic and GABAergic transmission. NPS exerts antidepressant-like effects by attenuating hyperactivity of the hypothalamicpituitary- adrenal (HPA) axis, modulating corticotropin-releasing factor (CRF) signalling, and influencing monoaminergic systems. Evidence indicates that EE may enhance NPS receptor (NPSR1) expression and downstream intracellular calcium signalling, reinforcing adaptive plasticity in the striatum and prefrontal cortex regions vulnerable in HD.
CONCLUSION: Integrating EE with NPS-targeted therapy could provide a multimodal approach to restore molecular homeostasis and alleviate depressive phenotypes in HD. Further research should elucidate optimal intervention timing, dose-response relationships, and potential cross-talk between EE-induced BDNF pathways and NPS-mediated stress resilience for translational application in neurodegenerative depression.
Tremor Other Hyperkinet Mov (N Y). 2026 Mar 13;16:16. doi: 10.5334/tohm.1161. eCollection 2026.ABSTRACTBACKGROUND: Musician's dystonia (MD) is a task-specific movement disorder affecting up to 1%...
Front Psychol. 2026 Feb 26;17:1704951. doi: 10.3389/fpsyg.2026.1704951. eCollection 2026.ABSTRACTINTRODUCTION: Psychodynamic group therapy (PDGT) for schizophrenia offers a therapeutic space where patients can explore conflicts considered...
Front Psychol. 2026 Feb 26;17:1654996. doi: 10.3389/fpsyg.2026.1654996. eCollection 2026.ABSTRACTOBJECTIVE: Reliable and accurate measurement is fundamental to scientific progress; however, the dominant measurement practices in psychology,...
Front Psychol. 2026 Feb 27;17:1753662. doi: 10.3389/fpsyg.2026.1753662. eCollection 2026.ABSTRACTThe term addiction or addictive disorder refers to a psychiatric condition that is characterized impulsive and compulsive...
SAGE Open Med Case Rep. 2026 Mar 10;14:2050313X261415610. doi: 10.1177/2050313X261415610. eCollection 2026.ABSTRACTDrug reaction with eosinophilia and systemic symptoms is a severe cutaneous adverse reaction frequently...
Cureus. 2026 Feb 12;18(2):e103466. doi: 10.7759/cureus.103466. eCollection 2026 Feb.ABSTRACTINTRODUCTION: NHS (National Health Service) waiting times and workforce pressures have increased in recent years, alongside growth...
