title: Signalling through phospholipase C beta 4 is not essential for midbrain dopaminergic neuron survival.
abstract: The most prominent progressive neurodegenerative movement disorder, Parkinson's disease, is attributed to selective loss of dopamine neurons in the substantia nigra pars compacta, resulting in severe deficiency of dopamine. The homeo-domain gene, Pit x 3, is essential for proper development of midbrain dopaminergic neurons in the substantia nigra pars compacta and might be involved in midbrain dopaminergic survival pathways. The mGluR1-signaling downstream-effector phospholipase C beta 4 was identified in a suppression subtractive hybridization screen comparing wild-type and Pit x 3-deficient Aphakia midbrain dopaminergic neurons. Expression pattern analysis revealed that phospholipase C beta 4 was expressed in midbrain dopaminergic neurons of the substantia nigra pars compacta and part of the ventral tegmental area, whereas expression of mGluR1alpha was predominantly observed in the more vulnerable midbrain dopaminergic neurons in the lateral substantia nigra pars compacta. However, clear expression of phospholipase C beta 4 in spared midbrain dopaminergic neurons of Aphakia mice located in the ventral tegmental area, indicated that induction and maintenance of phospholipase C beta 4 expression is Pit x 3-independent in these neurons. Furthermore, we report here a normal distribution of midbrain dopaminergic cell bodies and axonal projection to the striatum in phospholipase C beta 4-/- mice, indicating that signaling of phospholipase C beta 4 is not essential for the survival of midbrain dopaminergic neurons.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Smits
authors.forename: S
authors.initials: S
authors.lastname: van der Nobelen
authors.forename: K J M
authors.initials: KJ
authors.lastname: Hornman
authors.forename: L
authors.initials: L
authors.lastname: von Oerthel
authors.forename: J P H
authors.initials: JP
authors.lastname: Burbach
authors.forename: M P
authors.initials: MP
authors.lastname: Smidt
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D054799:Phospholipase C beta; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution; D010738:Type C Phospholipases / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518043:Plcb4 protein, mouse; D004298:Dopamine