Lack of dopaminergic inputs elongates the primary cilia of striatal neurons.
In the rodent brain, certain G protein-coupled receptors and adenylyl cyclase type 3 are known to localize to the neuronal primary cilium, a primitive sensory organelle protruding singly from almost all neurons. A recent chemical screening study demonstrated that many compounds targeting dopamine receptors regulate the assembly of Chlamydomonas reinhardtii flagella, structures which are analogous to vertebrate cilia. Here we investigated the effects of dopaminergic inputs loss on the architecture of neuronal primary cilia in the rodent striatum, a brain region that receives major dopaminergic projections from the midbrain. We first analyzed the lengths of neuronal cilia in the dorsolateral striatum of hemi-parkinsonian rats with unilateral lesions of the nigrostriatal dopamine pathway. In these rats, the striatal neuronal cilia were significantly longer on the lesioned side than on the non-lesioned side. In mice, the repeated injection of reserpine, a dopamine-depleting agent, elongated neuronal cilia in the striatum. The combined administration of agonists for dopamine receptor type 2 (D2) with reserpine attenuated the elongation of striatal neuronal cilia. Repeated treatment with an antagonist of D2, but not of dopamine receptor type 1 (D1), elongated the striatal neuronal cilia. In addition, D2-null mice displayed longer neuronal cilia in the striatum compared to wild-type controls. Reserpine treatment elongated the striatal neuronal cilia in D1-null mice but not in D2-null mice. Repeated treatment with a D2 agonist suppressed the elongation of striatal neuronal cilia on the lesioned side of hemi-parkinsonian rats. These results suggest that the elongation of striatal neuronal cilia following the lack of dopaminergic inputs is attributable to the absence of dopaminergic transmission via D2 receptors. Our results provide the first evidence that the length of neuronal cilia can be modified by the lack of a neurotransmitter's input.
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Japan; Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ko
K
Miyoshi
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kyosuke
K
Kasahara
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shinki
S
Murakami
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Mika
M
Takeshima
Department of Neurobiology and Anatomy, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Natsuko
N
Kumamoto
Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara, Japan.
Asako
A
Sato
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ikuko
I
Miyazaki
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Japan; Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
Shinsuke
S
Matsuzaki
Department of Comparative and Experimental Medicine Center for Bioresource-based Researches, Brain Research Institute, Niigata University, Niigata, Japan.
Toshikuni
T
Sasaoka
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Japan.
Taiichi
T
Katayama
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Masato
M
Asanuma
D000818:Animals; D001253:Astrocytes / Q000473:pathology; D048430:Cell Shape; D002923:Cilia / Q000473:pathology*; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000473:pathology; D066328:Ventral Striatum / Q000473:pathology*
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D012110:Reserpine