Partial�decortication ameliorates dopamine depletion‑induced striatal neuron lesions in rats

Abstract

The balance between glutamate (cortex and thalamus) and dopamine (substantia nigra) inputs on striatal neurons is of vital importance. Dopamine deficiency, which breaks this balance and leads to the domination of cortical glutamatergic inputs, plays an important role in Parkinson's disease (PD). However, the exact impact on striatal neurons has not been fully clarified. Thus, the present study aimed to characterize the influence of corticostriatal glutamatergic inputs on striatal neurons after decortication due to dopamine depletion in rats. 6-Hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid into the primary motor cortex to induce decortication. Subsequently, the grip strength test and Morris water maze task indicated that decortication significantly shortened the hang time and the latency that had been increased in the rats subjected to dopamine depletion. Golgi staining and electron microscopy analysis showed that the total dendritic length and dendritic spine density of the striatal neurons were decreased in the dopamine-depleted rats, whereas decortication alleviated this damage. Immunohistochemistry analysis demonstrated that decortication decreased the number of caspase-3-positive neurons in the dopamine-depleted rats. Moreover, reverse transcription-quantitative PCR and western blot analyses showed that decortication offset the upregulation of caspase-3 at both the protein and mRNA levels in the dopamine-depleted rats. In conclusion, the present study demonstrated that a relative excess of cortical glutamate inputs had a substantial impact on the pathological processes of striatal neuron lesions in PD.

The impact of Parkinson’s disease on striatal network connectivity and cortico-striatal drive: an in-silico study

“…It is worth mentioning that glutamate signaling contributes to the degeneration. Indeed, decortication (in rodents models) counteracts the morphological alterations (Zhu et al (2019)). In healthy conditions a transient dopamine increase enhances the excitability of dSPN via D1 dopamine receptor signalling, while it decreases the excitability of iSPN through D2 dopamine receptor signalling (Surmeier, Graves, and Shen (2014)).…”

“…We also predicted that chronic dopamine depletion in PD significantly increases the effective glutamatergic drive, especially to iSPNs. The glutamatergic hyperactivity is one significant driver of several of the morphological changes seen (Zhu et al (2019)). Targeting some of the most contributing factors may be relevant for counteracting PD progression.…”