Bellissimo 2023 Exp Physiol

Bellissimo CA, Castellani LN, Finch MS, Murugathasan M, Gandhi S, Sweeney G, Abdul-Sater AA, MacPherson REK, Perry CGR (2023) Memory impairment in the D2.mdx mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688. https://doi.org/10.1113/ep091274

» Exp Physiol 108:1108-17. PMID: 37415288 Open Access

Bellissimo Catherine A, Castellani Laura N, Finch Michael S, Murugathasan Mayoorey, Gandhi Shivam, Sweeney Gary, Abdul-Sater Ali A, MacPherson Rebecca EK, Perry Christopher GR (2023) Exp Physiol

Abstract: What is the central question of this study? Can adiponectin receptor agonism improve recognition memory in a mouse model of Duchenne muscular dystrophy? What is the main finding and its importance? Short-term treatment with the new adiponectin receptor agonist ALY688 improves recognition memory in D2.mdx mice. This finding suggests that further investigation into adiponectin receptor agonism is warranted, given that there remains an unmet need for clinical approaches to treat this cognitive dysfunction in people with Duchenne muscular dystrophy.

Memory impairments have been well documented in people with Duchenne muscular dystrophy (DMD). However, the underlying mechanisms are poorly understood, and there is an unmet need to develop new therapies to treat this condition. Using a novel object recognition test, we show that recognition memory impairments in D2.mdx mice are completely prevented by daily treatment with the new adiponectin receptor agonist ALY688 from day 7 to 28 of age. In comparison to age-matched wild-type mice, untreated D2.mdx mice demonstrated lower hippocampal mitochondrial respiration (carbohydrate substrate), greater serum interleukin-6 cytokine content and greater hippocampal total tau and Raptor protein contents. Each of these measures was partly or fully preserved after treatment with ALY688. Collectively, these results indicate that adiponectin receptor agonism improves recognition memory in young D2.mdx mice. • Keywords: Duchenne muscular dystrophy, Cognition, Memory, Mitochondria • Bioblast editor: Plangger M • O2k-Network Lab: CA Toronto Bellissimo C, CA Toronto Perry CG

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Myopathy 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Permeabilized cells 

Coupling state: LEAK, OXPHOS  Pathway: N  HRR: Oxygraph-2k 

2023-07