RESPONSE OF CDNF IN NUCLEUS ACCUMBENS CORE IN MICE OF BOTH SEXES: CELLULAR AND NEUROANATOMICAL LOCALIZATION

Cerebral Dopamine Neurotrophic Factor (CDNF) is an atypical neurotrophin with protective effects on dopaminergic neurons and has been proposed as a promising therapeutic candidate for neurodegenerative disorders such as Parkinson’s disease. However, its expression and function within the mesocorticolimbic system remain poorly understood. The nucleus accumbens (NAcb) Core is a key structure involved in regulating motivation, behavioral activation, and effort-related processes. In the present study, we investigated whether manipulations of the dopaminergic system modulate CDNF immunoreactivity in the NAcb Core of male and female mice using peroxidative and immunofluorescence techniques. CDNF localization was examined using cytological markers (DAPI, NeuN, and GFAP), presynaptic dopaminergic markers, and markers of postsynaptic GABAergic neuronal populations. Our results indicate that CDNF is localized in postsynaptic neuronal somas expressing Substance P, Enkephalin, and Parvalbumin, but not in dopaminergic terminals positive for tyrosine hydroxylase (TH) or dopamine transporter (DAT). Pharmacological dopamine depletion significantly reduced CDNF immunoreactivity in both sexes. Conversely, physical activity increased CDNF levels in males, whereas in females this increase was observed only after active operant training and not after wheel-running activity. Overall, these findings enhance our understanding of CDNF distribution and regulation in the mesocorticolimbic system and support the potential role of neurotrophic factors as innovative therapeutic targets for neuropsychiatric symptoms. Moreover, they highlight the importance of maintaining an active lifestyle to promote optimal brain function and neural plasticity.

Grant support: Ministerio de Ciencia e Innovación. PID2021-125977OB-I00.
Personal fellowship: FPU21/01105