RESUMO
Hearing requires the transduction of vibrational forces by specialized epithelial cells in the cochlea known as hair cells. The human ear contains a finite number of terminally differentiated hair cells that, once lost by noise-induced damage or toxic insult, can never be regenerated. We report here that sphingosine 1-phosphate (S1P) signaling, mainly via activation of its cognate receptor S1P2, is required for the maintenance of vestibular and cochlear hair cells in vivo. Two S1P receptors, S1P2 and S1P3, were found to be expressed in the cochlea by reverse transcription-PCR and in situ hybridization. Mice that are null for both these receptors uniformly display progressive cochlear and vestibular defects with hair cell loss, resulting in complete deafness by 4 weeks of age and, with complete penetrance, balance defects of increasing severity. This study reveals the previously unknown role of S1P signaling in the maintenance of cochlear and vestibular integrity and suggests a means for therapeutic intervention in degenerative hearing loss.
Assuntos
Células Ciliadas Auditivas/citologia , Receptores de Lisoesfingolipídeo/fisiologia , Estimulação Acústica , Envelhecimento/patologia , Animais , Sobrevivência Celular , Cóclea/crescimento & desenvolvimento , Cóclea/metabolismo , Cóclea/patologia , Cóclea/fisiopatologia , Surdez/genética , Surdez/patologia , Comportamento Exploratório , Células Ciliadas Auditivas/fisiologia , Células Ciliadas Vestibulares/citologia , Células Ciliadas Vestibulares/fisiologia , Audição/fisiologia , Hibridização In Situ , Lisofosfolipídeos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Órgão Espiral/metabolismo , Órgão Espiral/patologia , Equilíbrio Postural/fisiologia , Receptores de Lisoesfingolipídeo/biossíntese , Receptores de Lisoesfingolipídeo/deficiência , Receptores de Lisoesfingolipídeo/genética , Reflexo de Sobressalto , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transtornos de Sensação/genética , Transtornos de Sensação/patologia , Esfingosina/análogos & derivados , Receptores de Esfingosina-1-Fosfato , Gânglio Espiral da Cóclea/metabolismo , Gânglio Espiral da Cóclea/patologia , Vestíbulo do Labirinto/metabolismo , Vestíbulo do Labirinto/patologia , Vestíbulo do Labirinto/fisiopatologiaRESUMO
BACKGROUND: We investigated the influences of hyperbaric oxygen (HBO(2)) on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and blood glucose level (BGL). METHODS: Forty one patients with hypertension (HTN), diabetes mellitus (DM), HTN and DM and/or no HTN or DM underwent HBO(2) sessions (15-40 sessions for each patient). SBP, DBP, HR and BGL (for diabetics) were recorded before and after each session. RESULTS: HBO(2) caused significant elevation in SBP (11%) and DBP (12%) and a decrease in HR (18%) (p <0.001). Patients with DM and HTN showed higher elevation in SBP and DBP. HBO(2) lowered BGL by 23% (p <0.001). When basal BGL was in the range of 120-170 mg/dl, it dropped to <100 mg/dl in 31/60 treatment sessions (52%). When basal BGL was <120 mg/dl it dropped to <70 mg/dl in 8/34 sessions. There was a possibility of lowered BGL when basal BGL was <170 mg/dl and a marked reduction in BGL occurred when basal BGL was <120 mg/dl. HBO(2) caused a marked elevation in SBP and DBP when basal SBP was >140 mmHg. Critical elevation was obtained when SBP was >160 mmHg. The use of beta blockers caused significant elevation of blood pressure while reducing HR. CONCLUSIONS: HBO(2) causes elevation of blood pressure and lowering of HR and BGL, which were augmented in the presence of HTN, DM, or beta blocker. The use of beta blockers for the management of HTN should be avoided during HBO(2) therapy.