Numerous in vitro and in vivo models of Parkinson’s disease (PD) demonstrate that pituitary adenylate cyclase-activating polypeptide (PACAP) conveys its strong neuroprotective actions mainly via its specific PAC1 receptor (PAC1R) in models of PD. We recently described the decrease in PAC1R protein content in the basal ganglia of macaques in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD that was partially reversed by levodopa therapy. In this work, we tested whether these observations occur also in the rotenone model of PD in the rat. The rotarod test revealed motor skill deterioration upon rotenone administration, which was reversed by benserazide/levodopa (B/L) treatment. The sucrose preference test suggested increased depression level while the open field test showed increased anxiety in rats rendered parkinsonian, regardless of the received B/L therapy. Reduced dopaminergic cell count in the substantia nigra pars compacta (SNpc) diminished the dopaminergic fiber density in the caudate-putamen (CPu) and decreased the peptidergic cell count in the centrally projecting Edinger–Westphal nucleus (EWcp), supporting the efficacy of rotenone treatment. RNAscope in situ hybridization revealed decreased PACAP mRNA (Adcyap1) and PAC1R mRNA (Adcyap1r1) expression in the CPu, globus pallidus, dopaminergic SNpc and peptidergic EWcp of rotenone-treated rats, but no remarkable downregulation occurred in the insular cortex. In the entopeduncular nucleus, only the Adcyap1r1 mRNA was downregulated in parkinsonian animals. B/L therapy attenuated the downregulation of Adcyap1 in the CPu only. Our current results further support the evolutionarily conserved role of the PACAP/PAC1R system in neuroprotection and its recruitment in the development/progression of neurodegenerative states such as PD.

Parkinson’s disease (PD) is an age-associated neurodegenerative disorder in which affective non-motor symptoms substantially contribute to disease burden, yet their neurobiological basis remains incompletely understood. We investigated region-specific alterations of corticotropin-releasing hormone (CRH) family neuropeptides in a rotenone-induced rat model of PD and evaluated the effects of combined dopaminergic (benserazide/L-DOPA) and antidepressant (fluoxetine) treatment. Motor performance, anhedonia-like behavior, dopaminergic neurodegeneration, and CRH-, urocortin 1 (UCN1)-, urocortin 2 (UCN2)-, and urocortin 3 (UCN3)-related molecular changes were assessed using behavioral testing, immunohistochemistry, and RNAscope in situ hybridization. Rotenone treatment induced robust motor impairment, nigral dopaminergic neurodegeneration with α-synuclein-positive Lewy body-like inclusions, and anhedonia-like behavior. Combined dopaminergic–antidepressant therapy improved affective deficits without reversing dopaminergic neuronal loss. Region-specific analyses revealed pronounced dysregulation of hypothalamic and midbrain stress-related neuropeptide systems, including the paraventricular nucleus/CRH, paraventricular nucleus/UCN2, lateral hypothalamic area/UCN3, and centrally projecting Edinger-Westphal nucleus/UCN1, whereas CRH- and UCN3-expressing populations within the extended amygdala remained largely unaffected. Correlation analyses further supported coordinated regulation among hypothalamic CRH-family systems and their association with affective behavioral alterations. These findings identify selective vulnerability of hypothalamic stress-regulatory neuropeptide circuits in experimental PD and suggest that aging-related impairment of stress resilience may contribute to affective non-motor symptoms. Beyond providing a comprehensive neuroanatomical characterization of CRH-family peptide alterations, this work highlights region-specific neuropeptide signaling as a potential framework for developing more precise biomarkers and targeted therapeutic strategies for PD-associated mood disturbances.

Objectives: The aim of this study was to evaluate the reliability, accuracy, and morbidity of dynamic sentinel lymph node biopsy (DSNB) in patients with intermediate- and high-risk penile cancer who had clinically negative lymph nodes, with a focus on long-term follow-up outcomes. Methods: Between January 2005 and January 2024, 287 patients with histologically confirmed penile cancer underwent radioisotope-guided DSNB at the Department of Urology, University of Pécs. Patients lost to follow-up within 24 months were excluded. Of the remaining patients, 211 underwent primary DSNB and 37 secondary DSNB. Thirty-nine patients in the primary DSNB group with Tis, T1a, or G1 tumours were additionally excluded, leaving 209 patients for analysis. Variables included tumour stage and grade, sentinel lymph node (SLN) yield and histology, complications, inguinal progression, false-negative rate, and radical lymphadenectomy findings. Results: A total of 573 SLNs were removed from 209 patients, with a median of 2.7 nodes per patient. SLN metastases were identified in 31 patients, involving 37 groins. Among 178 patients with negative SLNs, three developed inguinal metastases. Sensitivity was 91% per patient and 92.5% per groin, with false-negative rates of 8% and 7.5%, respectively. All false-negative cases occurred within two years, with no later inguinal recurrences. DSNB-related complications occurred in 24 patients (11.4%); most were mild or moderate and managed on an outpatient basis. Two patients required surgery and one required hospital readmission. Conclusions: In a high-volume centre, DSNB is a safe and reliable staging procedure with low morbidity in clinically node-negative intermediate- and high-risk penile cancer. Further studies should assess radiotracer injection sites and compare one-day versus two-day protocols.