In Vivo Electrochemical Aptasensors Reveal Reversible Dopamine Dysregulation from Adolescent Malnutrition

Dopamine (DA) signaling is essential for neurodevelopment and is particularly sensitive to disruption during adolescence. Protein restriction (PR) can impair DA dynamics, yet mechanistic insights remain limited due to challenges in real-time neurochemical sensing. Here, we present aptCFE_DA3.0, a robust implantable aptamer-based sensor fabricated via a reagent-free, 3 min electrochemical conjugation (E-conjugation) using amine-quinone chemistry. This nanobio interface engineering strategy enables stable, hydrolysis-resistant aptamer attachment for reliable in vivo DA monitoring. AptCFE_DA3.0 exhibits a 30% higher sensitivity compared with bare electrodes over 0.5-20 μM DA, maintains over 80% of its response after 24 h in bovine serum albumin (BSA), and shows high selectivity for DA. Using this platform, we show that adolescent PR reduces DA release by ∼80% in the nucleus accumbens and doubles DA reuptake time in the dorsal striatum, with minimal effects observed in adults. Nanoelectrochemical and single-cell analyses reveal increased vesicular catecholamine content and prolonged fusion pore opening during exocytosis. Notably, dietary intervention partially restores DA signaling, underscoring adolescent neural plasticity. These findings highlight the power of advanced neurochemical tools for dissecting nutrition-sensitive neurotransmission and forming strategies for neurodevelopmental disorders.