Objective: To examine associations between serum-derived adult hippocampal neurogenesis (AHN)¹ markers and cognitive and neuropsychiatric symptoms in Parkinson’s disease (PD), and to explore whether a dance-based intervention (PD-Ballet^TM) modifies these cellular phenotypes

Background: AHN is implicated in cognitive and neuropsychiatric regulation^{2, 3} yet remains poorly understood in PD⁴. Physical activity is proposed to influence AHN⁵, but the clinical relevance of these mechanisms and their responsiveness to behavioural interventions in PD are unclear.

Method: MemHiN is a mechanistic sub-study within a controlled single-blinded trial (PD-Ballet^TM Study) in which participants were randomised 2:1 to a 12-week dance-based programme delivered by the English National Ballet, or usual care with social control⁶. Serum collected at baseline and post-intervention was applied to human hippocampal progenitor cells to quantify proliferation and differentiation markers [nestin, SOX2, Ki67, cleaved caspase-3 (CC3), doublecortin (DCX), MAP2, cell count] using an immunocytochemistry assay⁷. Baseline associations with Montreal Cognitive Assessment, Hopkins Verbal Learning Test-Revised (HVLT-R), Mnemonic Similarity Task (MST) and Movement Disorder Society Non-Motor Scale (MDS-NMS) domains were examined using covariate-adjusted regression with false discovery rate correction. Intervention effects were assessed using mixed-effects models.

Results: Serum samples were available from 29 participants at baseline (active n=19; control n=10) and 21 post-intervention. At baseline, lower progenitor marker expression (Nestin) was associated with greater depressive symptom burden, while higher apoptotic marker expression (CC3) was associated with more severe psychosis domain scores (false discovery rate-corrected p<0.05). Nominal associations were observed between differentiation markers and verbal memory (MAP2 and DCX with HVLT-R), and between pattern separation (MST lure discrimination index) and cell count. No significant group-by-time effects in relation to the intervention were detected for AHN markers.

Conclusion: Serum-induced AHN phenotypes are associated with neuropsychiatric symptom burden in PD, particularly depressive and psychotic symptoms. Short-term participation in a dance-based intervention did not significantly modify proliferation or differentiation markers.

References: 1. Doludda B, Barde W, D’Egidio F, et al. Adult neurogenesis: New neurons, new opportunities. Cell Stem Cell 2026;33:382-392.
2. Du Preez A, Lefèvre-Arbogast S, González-Domínguez R, et al. Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing. Age Ageing 2024;53:ii47-ii59.
3. Berger T, Lee H, Young AH, Aarsland D, Thuret S. Adult Hippocampal Neurogenesis in Major Depressive Disorder and Alzheimer’s Disease. Trends Mol Med 2020;26:803-818.
4. Regensburger M, Prots I, Winner B. Adult hippocampal neurogenesis in Parkinson’s disease: impact on neuronal survival and plasticity. Neural Plast 2014;2014:454696.
5. Farmand S, Du Preez A, Kim C, et al. Cognition on the move: Examining the role of physical exercise and neurogenesis in counteracting cognitive aging. Ageing Research Reviews 2025;107:102725.
6. Podlewska AM, Batzu L, Soukup T, et al. The PD-Ballet study: study protocol for a randomised controlled single-blind hybrid type 2 clinical trial evaluating the effects of ballet dancing on motor and non-motor symptoms in Parkinson’s disease. BMC Complement Med Ther 2024;24:41.
7. de Lucia C, Murphy T, Maruszak A, et al. Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells. Aging Dis 2021;12:2151-2172.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/adult-hippocampal-neurogenesis-and-cognitive-and-neuropsychiatric-symptoms-in-parkinsons-disease-the-memhin-study/