Abstract
Trefoil factor 1 (TFF1) belongs to a family of secreted peptides with a characteristic tree-looped trefoil structure. TFFs are mainly expressed in the gastrointestinal tract where they play a critical role in the function of the mucosal barrier. TFF1 has been suggested as a neuropeptide, but not much is known about its expression and function in the central nervous system. We investigated the expression of TFF1 in the developing and adult rat midbrain. In the adult ventral mesencephalon, TFF1-immunoreactive (-ir) cells were predominantly found in the substantia nigra pars compacta (SNc), the ventral tegmental area (VTA) and in periaqueductal areas. While around 90% of the TFF1-ir cells in the SNc co-expressed tyrosine hydroxylase (TH), only a subpopulation of the TH-ir neurons expressed TFF1. Some TFF1-ir cells in the SNc co-expressed the calcium-binding proteins calbindin or calretinin and nearly all were NeuN-ir confirming a neuronal phenotype, which was supported by lack of co-localization with the astroglial marker glial fibrillary acidic protein (GFAP). Interestingly, at postnatal (P) day 7 and P14, a significantly higher proportion of TH-ir neurons in the SNc co-expressed TFF1 as compared to P21. In contrast, the proportion of TFF1-ir cells expressing TH remained unchanged during postnatal development. Furthermore, significantly more TH-ir neurons expressed TFF1 in the SNc, compared to the VTA at all four time-points investigated. Injection of the tracer fluorogold into the striatum of adult rats resulted in retrograde labeling of several TFF1 expressing cells in the SNc showing that a significant fraction of the TFF1-ir cells were projection neurons. This was also reflected by unilateral loss of TFF1-ir cells in SNc of 6-hydroxylase-lesioned hemiparkinsonian rats. In conclusion, we show for the first time that distinct subpopulations of midbrain dopaminergic neurons express TFF1, and that this expression pattern is altered in a rat model of Parkinson’s disease.
Highlights
Idiopathic Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNc) within the ventral mesencephalon
In the ventral midbrain Trefoil factor 1 (TFF1) was markedly expressed in cells of the SN pars compacta (SNc) and the SN pars lateralis (SNl), and to a lesser extent in the ventral tegmental area (VTA), while SN pars reticulata (SNr) contained almost no TFF1-ir cells (Figure 2)
Quantification of the relative content of TFF1-ir cells that colocalized with tyrosine hydroxylase (TH) revealed no significant difference between the SN and VTA (Figure 3A) (SN: 89.6 ± 0.9 and VTA: 80.2 ± 5.0% TFF1 co-localization with TH; mean ± SEM; n = 4), whereas the percentage of TH-ir cells that co-localized with TFF1 was significantly higher in the SN as compared to the VTA (Figure 3B) (SN: 26.8 ± 1.5 and VTA: 13.1 ± 1.2% TH colocalization with TFF1; mean ± SEM; n = 4; P
Summary
Idiopathic Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNc) within the ventral mesencephalon. The cause of the selective loss of dopaminergic neurons remains largely unknown, several mechanisms have been proposed including oxidative stress, mitochondrial dysfunction and, excitotoxic damage [4]. Midbrain dopaminergic neurons represent a heterogeneous cell population that can be divided into three principal groups; those of the the retrorubral area, SNc and the ventral tegmental area (VTA), classified as the A8, A9 and A10 cell groups, respectively [5]. Expression of TFF1 mRNA in cultured mouse astrocytes has been found in the late G1 or early S phase under regulation of cytokines, such as IL-6, IL-7, and TNF-α [28,29]. With the aim to test TFF1 as a potential supplementary marker of subsets of midbrain dopaminergic neurons we here investigated its expression in the developing and adult rat ventral mesencephalon by means of immunohistochemistry and retrograde tracing of nigrostriatal fibers. We studied the effects of unilateral, 6-hydroxydopamine (6-OHDA) lesions on the content and distribution of midbrain TFF1-ir cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
