Fos-enkephalin signaling in the rat medial vestibular nucleus facilitates vestibular compensation.
In the present study, we first observed up-regulation in preproenkephalin (PPE)-like immunoreactivity (-LIR), a precursor of Met- and Leu-enkephalin, in the rat ipsilateral medial vestibular nucleus (ipsi-MVN) after unilateral labyrinthectomy (UL). By means of double-staining immunohistochemistry with PPE and Fos, a putative regulator of PPE gene expression, we revealed that some of these PPE-LIR neurons were also Fos immunopositive. The time course of decay of these double-stained neurons was quite parallel to that of UL-induced behavioral deficits. This suggests that these double-labeled neurons could have something to do with development of vestibular compensation. We next examined correlation between Fos and PPE expression in the ipsi-MVN by means of a 15-min pre-UL application of antisense oligonucleotide probes against c-fos mRNA into the ipsi-MVN. Gel shift assay and Western blotting revealed that elimination of Fos expression significantly reduced both AP-1 DNA binding activity and PPE expression in the ipsi-MVN after UL. C-fos antisense study also revealed that depression of Fos-PPE signaling in the ipsi-MVN caused significantly more severe behavioral deficits during vestibular compensation. Furthermore, studies with PPE antisense and naloxone, an opioid receptor antagonist, demonstrated that specific depression of enkephalinergic effects in the ipsi-MVN significantly delayed vestibular compensation. All these findings suggest that, immediately after UL, Fos induced in some of the ipsi-MVN neurons could regulate consequent PPE expression via the AP-1 activation and facilitate the restoration of balance between bilateral MVN activities via the opioid receptor activation, resulting in progress of vestibular compensation.
Kitahara
Tadashi
T
Department of Otolaryngology, Osaka University, School of Medicine, Osaka, Japan. tkitahara@ent.med.osaka-u.ac.jp
Kaneko
Takeshi
T
Horii
Arata
A
Fukushima
Munehisa
M
Kizawa-Okumura
Kaoru
K
Takeda
Noriaki
N
Kubo
Takeshi
T
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D004745:Enkephalins / Q000378:metabolism*; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D004856:Postural Balance / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D015837:Vestibular Diseases / Q000378:metabolism* / Q000503:physiopathology; D014726:Vestibular Nuclei / Q000378:metabolism* / Q000503:physiopathology
D004745:Enkephalins; D016376:Oligonucleotides, Antisense; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011957:Receptors, Opioid; D018808:Transcription Factor AP-1; C033660:preproenkephalin