ArticleFrontiers in aging neuroscience2026
Intracisternal IGF-1 gene delivery attenuates early anxiety-like behavior but not dopaminergic neurodegeneration in a 6-OHDA rat model of parkinsonism.
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to a spectrum of motor and non-motor symptoms. In addition to the motor deficits serving as the primary criteria for diagnosis, mood and anxiety disorders also play a significant role in shaping the prognosis and overall disease progression in PD. Objectives: In this study, our aim was to characterize the progression of anxiety-like behavioral deficits in a rat model of neurotoxicity induced by 6-hydroxydopamine (6-OHDA) and to investigate insulin-like growth factor 1 (IGF-1) potential therapeutic effects on these pathological markers. Methods: Behavioral changes were evaluated in male Wistar rats at 1, 2, and 3 weeks post-lesion using the elevated plus maze and dark-light box tests. Anxiety-like behaviors emerged as early as week 1 post-lesion and persisted through week 3. Following 6-OHDA infusion, immunohistochemical analysis revealed a decrease in tyrosine hydroxylase (TH) immunoreactivity within the ventral tegmental area (VTA) indicating a partial lesion of the nigrostriatal dopaminergic system. As a therapeutic approach we performed the intracisternal administration of a recombinant adenoviral vector encoding IGF-1 (RAd IGF-1) one week after 6-OHDA-induced neurotoxicity. Results: At a behavioral level, IGF-1 treatment effectively prevented anxiety-like behavior by the third week of neurotoxicity. Nevertheless, IGF-1 overexpression was not able to modulate VTA dopaminergic neuron loss. These results reveal a dissociation between the behavioral effects of IGF-1 and its impact on dopaminergic neurodegeneration. Discussion: These findings emphasize time-dependent alterations in anxiety-like behavior and dopaminergic neurodegeneration. In addition, these data support the potential use of IGF-1 as a therapeutic molecule and its novel administrations for future gene transfer interventions, which will shed light on the progressive nature of neurodegenerative mechanisms.
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