Dopaminergic cells in the periaqueductal grey matter of MPTP-treated monkeys and mice; patterns of survival and effect of deep brain stimulation and lesion of the subthalamic nucleus☆

Abstract 

In this anatomical study, we have examined the number of tyrosine hydroxylase (TH) cells in the periaqueductal grey matter (PAG) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and mice; further, we explored whether kainic acid lesion or deep brain stimulation (DBS) of the subthalamic nucleus (STN) in MPTP-treated monkeys has any impact on the number of TH⁺ cells in the PAG. For monkeys, there were four groups: Normal, MPTP, STN-lesioned (+MPTP) and STN-DBS (+MPTP). For mice, BALB/c albino mice were divided into three groups, Saline, MPTP_50 (50 mg/kg), MPTP_100 (100 mg/kg). Animals were perfused transcardially with aldehyde fixative 6–12 days after their last MPTP injection. Brains were processed for immunochemistry and the number of cells was estimated using the optical fractionator method. Our results revealed significant reductions (25–30%) in TH⁺ cell number in the PAG of MPTP-treated monkeys and mice compared to controls. These reductions were not as substantial as those recorded in the SNc in the same animals (40–60%). Further, in monkeys, there were significantly more TH⁺ cells in the PAG of STN-lesioned and STN-DBS groups compared to the MPTP group. In fact, the number of TH⁺ cells in the STN alteration cases were similar to the Normal group. In summary, our results indicated that MPTP is toxic to TH⁺ cells in the PAG of monkeys and mice and that in monkeys, lesion or DBS of the STN offers neuroprotection against this toxicity.

Keywords: Brainstem, Tyrosine hydroxylase, Cell death, Substantia nigra, Parkinson disease

Abbreviations: Cu, cuneiform nucleus, DBS, deep brain stimulation, DL, dorsolateral subdivision of the periaqueductal grey matter, DM, dorsomedial subdivision of the periaqueductal grey matter, ICol, inferior colliculus, L, lateral subdivision of the periaqueductal grey matter, MAq, mesencephalic aqueduct, MG, medial geniculate nucleus, MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, PAG, periaqueductal grey matter, PBS, phosphate-buffered saline, Pn, Pontine nuclei, PpT, pedunculopontine tegmental nucleus, Pul, pulvinar, R, red nucleus, SCol, superior colliculus, scp, superior cerebellar peduncle, SNc, substantia nigra pars compacta, STN, subthalamic nucleus, TH, tyrosine hydroxylase, VL, ventrolateral subdivision of the periaqueductal grey matter, VTA, ventral tegmental area