The substantia nigra pars compacta of the Göttingen minipig: an anatomical and stereological study

Abstract

Parkinson disease (PD) is a neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Despite advances in medical and surgical therapies, many PD patients experience progression of their symptoms and medical side effects over time. To explore new treatments, new animal models mimicking the progressive PD nature are needed. The pig is well suited for this purpose with its large gyrated brain, sensitive to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The objective of this study was to provide the anatomical foundation for such a model, describing in detail the SNc in normal Göttingen minipigs and estimating the volume and total number of tyrosine hydroxylase (TH)-positive neurons. The brain stems of 6 Göttingen minipigs were paraffin embedded and serially cut before Nissl staining and immunohistochemical visualization of TH. The volume of the SNc and the total number of TH-positive neurons were estimated by design-based stereology. The substantia nigra was located at the dorsal rim of the crus cerebri extending throughout the mesencephalon. A dorsal pars compacta and a ventral pars reticulata were demonstrated. The SNc merged with the ventral tegmental area medially and the retro-rubral field dorsocaudolaterally. The total number of TH-positive neurons in the SNc unilaterally was estimated to 80,700 [74,100;87,300], and the volume estimate was 26.4 mm(3) [25.0;27.8]. We conclude that the anatomy of the SNc in the Göttingen minipig corresponds well with that of higher primates, and is well suited for further studies aimed at optimizing this non-primate large animal model for PD.

Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals

“…We have recently confirmed our MR image-guided targeting system and fMRI group analysis method in Yucatan minipigs (data not included) for which there is a PD model available (Bjarkam et al, 2008; Nielsen et al, 2009). The work reported here, thus sets the stage for future investigations that combine functional neuroimaging with electrical stimulation in a chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) PD model.…”

The cytoarchitectonic and TH-immunohistochemical characterization of the dopamine cell groups in the substantia nigra, ventral tegmental area and retrorubral field in a bat (Artibeus planirostris)

“…Although dopaminergic groups have been studied in a few chiropteran species, A. planirostris is the first bat species to present this feature. The tSN has been described only in rodent species, the rock cavy (Kerodon rupestris) (Cavalcanti et al, 2014), and in the göttingen minipig (Susscrofa domesticus), a laboratory-developed artiodactylid derived from the domestic pig (Nielsen et al, 2009). To clarify its contribution to the modulation of the motor system, functional studies of the tSN are clearly necessary.…”

A three-dimensional digital segmented and deformable brain atlas of the domestic pig

“…The deep cerebral structures identified in this atlas were compared to the few pig brain atlases available in the literature (Felix et al, 1999;Salinas-Zeballos et al, 1986;Watanabe et al, 2001;Yoshikawa, 1968) in addition to the studies on specific subcortical areas such as the hypothalamus (Ettrup et al, 2010), the substantia nigra (Nielsen et al, 2009) and the subthalamic nucleus (Larsen et al, 2004). The sole valid source of comparison was represented by Felix's stereotaxic adult domestic pig brain atlas (Felix et al, 1999).…”