NeuralCipher Research overview
The text below is the source article’s original abstract under a verified reuse license. cc by
The subthalamic nucleus (STN), the main driving force of the basal ganglia, is innervated by brainstem serotonin (5-HT) neurons with highly plastic axonal arborization. A pathologically-induced rearrangement of the ascending 5-HT projections could contribute to the disrupted firing pattern of STN neurons observed in Parkinson's disease (PD). This light and electron microscope study was designed to characterize the neuroadaptive changes of 5-HT inputs to the different functional territories of the STN in four cynomolgus monkeys (Macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and four control animals. Using an unbiased stereological approach, we report a significant decrease of the density of 5-HT axon varicosities immunolabeled for the 5-HT membrane transporter (SERT), across all STN functional territories of MPTP-treated monkeys. In MPTP-treated animals, the SERT+ axon varicosities are larger than in control monkeys. In both experimental conditions they are only partially synaptic. A preserved length of 5-HT axons in the STN along with a conserved number of 5-HT neurons in the dorsal raphe nucleus is observed. Overall, our results indicate that, in parkinsonian monkeys, the 5-HT axons projecting to the STN are preserved but endowed with significantly less axon varicosities. Such neuroadaptive change could lead to a lower ambient level of 5-HT in this basal ganglia component, representing a compensatory mechanism designed to cope with the hyperexcitability of STN neurons that is known to occur in PD.
Scientific assessment
Research question
Assess the question within the original study’s scope.
Methods & sample
Check the source article for study design and sample details.
Key findings
An editorially approved findings summary is not yet published for this record.
Limitations
Generalizability, bias and clinical meaning require separate assessment.
Methods, samples and clinical conclusions are not inferred from bibliographic metadata.