Dexmedetomidine Exerts Multi-level Effects to Ameliorate Alzheimer's Disease Pathology in the Adult Zebrafish Brain
MOLECULAR NEUROBIOLOGY, vol.63, no.1, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 63 Issue: 1
- Publication Date: 2026
- Doi Number: 10.1007/s12035-026-05906-9
- Journal Name: MOLECULAR NEUROBIOLOGY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- Dokuz Eylül University Affiliated: Yes
Abstract
Alzheimer's disease (AD) is a complex neurodegenerative condition involving beta-amyloid (A beta) deposition, tau abnormalities, neuroinflammation, neuronal degeneration, and progressive impairment of cognitive functions. Despite extensive research, effective disease-modifying therapies remain limited, highlighting the need for translationally relevant models and repurposable therapeutic candidates. Dexmedetomidine (DEX), an alpha 2-adrenergic receptor agonist with known neuroprotective properties, was investigated in an adult zebrafish model of AD established through cerebroventricular administration of A beta 42. DEX treatment significantly reduced A beta accumulation and was associated with reduced amyloidogenic gene expression, indicating transcriptional changes in amyloidogenic pathway-related genes. DEX attenuated neuroinflammation by reducing glial activation, lowering pro-inflammatory cytokine gene expression, and increasing expression of the anti-inflammatory gene il10. Immunofluorescence assessment further demonstrated reduced astrogliosis and preserved neuronal marker integrity, as indicated by increased HuC/D levels. Interestingly, DEX attenuated A beta-induced proliferative responses, characterized by decreased PCNA expression, while enhancing cleaved caspase-3 levels, suggesting changes in proliferation and apoptotic signaling under A beta stress conditions. Behavioral assessments further demonstrated that DEX alleviated A beta 42-induced anxiety- and aggression-like behaviors, improving behavioral phenotypes in this model. Overall, these findings underscore the multi-level effects of DEX in modulating AD-related pathological features. As a clinically available agent, DEX represents a promising candidate for repurposing in neurodegenerative disease contexts. Further preclinical studies in mammalian models are warranted to validate its translational relevance and therapeutic potential.