Recombinant bovine alphas1-casein ameliorates PCPA-induced insomnia-like behavioral and physiological abnormalities in mice

16/10/2026

AI Summary

Recombinant bovine αs1-casein (RC) ameliorated PCPA-induced insomnia-like behaviour and promoted body-weight recovery without affecting major-organ indices.
RC normalised brain monoamines and amino acid neurotransmitters, increasing 5-HT, 5-HIAA, dopamine, GABA and glutamate while reducing elevated norepinephrine.
High-dose RC lowered serum IL-6, preserved hippocampal morphology, and altered cecal microbiota richness and community structure implicating the microbiota-gut-brain axis.

TL;DR (AI Generated)

Recombinant bovine αs1-casein (RC) is a scalable milk-protein ingredient, but its effects on insomnia-like physiological and behavioral abnormalities have not been systematically evaluated.

The parallel physiological, neurochemical, inflammatory, and microbial changes support an association between RC administration and improvement of PCPA-induced insomnia-like abnormalities.

These results identify recombinant bovine αs1-casein as a promising food-derived ingredient for further investigation in sleep-health applications, while the microbiota-gut-brain axis is presented as a testable mechanistic framework rather than a demonstrated causal pathway.

Basic summary

Food Funct. 2026 Oct 15. doi: 10.1039/d6fo03828j. Online ahead of print.

ABSTRACT

Insomnia is a multifactorial sleep-wake disorder associated with altered neurotransmitter homeostasis, systemic inflammatory changes, and gut microbial dysbiosis. Recombinant bovine αs1-casein (RC) is a scalable milk-protein ingredient, but its effects on insomnia-like physiological and behavioral abnormalities have not been systematically evaluated. We investigated RC in a p-chlorophenylalanine (PCPA)-induced mouse model. Male ICR mice received RC (100, 300, or 500 mg kg^-1 day^-1), melatonin, Naoxinshu oral liquid, natural casein, or vehicle for 7 days after PCPA modeling. Body weight, open-field behavior, serum cytokines, brain neurotransmitters, hippocampal histology, organ indices, and cecal microbiota were assessed. RC improved body-weight recovery and open-field performance without altering major-organ indices. It increased brain 5-HT, 5-HIAA, dopamine, GABA, and glutamate concentrations and reduced the elevated norepinephrine concentration. High-dose RC reduced serum IL-6 and was associated with better-preserved hippocampal morphology. 16S rRNA gene sequencing showed RC-associated changes in bacterial richness and community structure. The parallel physiological, neurochemical, inflammatory, and microbial changes support an association between RC administration and improvement of PCPA-induced insomnia-like abnormalities. These results identify recombinant bovine αs1-casein as a promising food-derived ingredient for further investigation in sleep-health applications, while the microbiota-gut-brain axis is presented as a testable mechanistic framework rather than a demonstrated causal pathway.

PMID:42878146 | DOI:10.1039/d6fo03828j

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