Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion.
Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.
Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster University of Bern, Inselspital, CH-3010 Berne, Switzerland.
Rémy
R
Liechti
Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster University of Bern, Inselspital, CH-3010 Berne, Switzerland.
Angélique D
AD
Ducray
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Winsløwparken 21, DK-5000 Odense C, Denmark.
Pia
P
Jensen
Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster University of Bern, Inselspital, CH-3010 Berne, Switzerland.
Stefano
S
Di Santo
Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster University of Bern, Inselspital, CH-3010 Berne, Switzerland.
Stefanie
S
Seiler
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense C, Denmark; Department of Cardiovascular and Renal Research, University of Southern Denmark, Winsløwparken 21, DK-5000 Odense C, Denmark.
Charlotte H
CH
Jensen
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Winsløwparken 21, DK-5000 Odense C, Denmark.
Morten
M
Meyer
Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster University of Bern, Inselspital, CH-3010 Berne, Switzerland.
Hans Rudolf
HR
Widmer
D000818:Animals; D015415:Biomarkers; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D016627:Oxidopamine / Q000009:adverse effects; D010641:Phenotype; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; C512923:Dlk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase