Tracing melanin-concentrating hormone function: decades of memory research and emerging links to Alzheimer's disease
Abstract
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide classically implicated in the regulation of energy homeostasis, sleep-wake cycle and motivated behaviors. Over the last 30 years, an increasing amount of evidence has revealed a complex, non-linear role in memory processing. In this mini-review, we summarize experimental findings on the multifaceted influence of MCH on memory, highlighting how this neuropeptide can promote consolidation by improving synaptic efficacy, induce the forgetting of hippocampus-dependent memories during REM sleep or negatively regulate memory formation. We also discuss emerging evidence linking MCH dysregulation to the pathophysiology of Alzheimer's disease (AD). Early interest in MCH as a cerebrospinal fluid biomarker has been superseded by non-invasive blood assays. Recent data, however, suggest therapeutic potential and a unique pathological vulnerability. While emerging evidence suggests MCH somata may show early resilience, their axonal projections are severely compromised by amyloid pathology. Ultimately, tau pathology appears to drive late-stage somatic degeneration and reduced activation during REM sleep. Importantly, activating surviving MCH neurons has been shown to restore sleep architecture in preclinical models, offering a potential therapeutic target for sleep disturbances. In conclusion, decades of basic memory research together with human and preclinical studies identify the MCH system as an important neuromodulatory…
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