Abstract
Background: Patients with obstructive sleep apnoea syndrome (OSAS) often display persistent cognitive dysfunction despite effective treatment with continuous positive airway pressure (CPAP). Brain-derived neurotrophic factor (BDNF) is a key mediator of memory and cognition, but its regulation in OSAS and during CPAP treatment is unknown.
Methods: Serum and plasma BDNF concentrations, BDNF secretion by peripheral blood mononuclear cells, and overnight polysomnography were evaluated in 17 men with newly diagnosed OSAS (as defined by a respiratory disturbance index of >10/hour with >70% obstructive events and corresponding daytime symptoms) and 12 healthy control men. In the patients all the parameters were monitored after 1 night and 3 months of CPAP treatment.
Results: There was no significant difference in baseline serum BDNF, plasma BDNF, or spontaneous BDNF secretion by peripheral blood mononuclear cells between untreated patients and controls. After 1 night of CPAP treatment there was a steep fall in median serum BDNF (from 18.0 ng/ml to 4.1 ng/ml) and plasma BDNF (from 58.7 pg/ml to 22.0 pg/ml) concentrations. Following 3 months of treatment BDNF concentrations did not return to baseline. In contrast, BDNF secretion was not suppressed by CPAP treatment.
Conclusions: Patients with untreated OSAS have normal serum and plasma BDNF levels. CPAP treatment is associated with a rapid decrease in serum and plasma BDNF levels which may reflect enhanced neuronal demand for BDNF in this condition.
Full Text
The Full Text of this article is available as a PDF (124.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adrien Joëlle. Neurobiological bases for the relation between sleep and depression. Sleep Med Rev. 2002 Oct;6(5):341–351. [PubMed] [Google Scholar]
- Baldelli P., Novara M., Carabelli V., Hernández-Guijo J. M., Carbone E. BDNF up-regulates evoked GABAergic transmission in developing hippocampus by potentiating presynaptic N- and P/Q-type Ca2+ channels signalling. Eur J Neurosci. 2002 Dec;16(12):2297–2310. doi: 10.1046/j.1460-9568.2002.02313.x. [DOI] [PubMed] [Google Scholar]
- Beebe Dean W., Gozal David. Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep Res. 2002 Mar;11(1):1–16. doi: 10.1046/j.1365-2869.2002.00289.x. [DOI] [PubMed] [Google Scholar]
- Chen B., Dowlatshahi D., MacQueen G. M., Wang J. F., Young L. T. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001 Aug 15;50(4):260–265. doi: 10.1016/s0006-3223(01)01083-6. [DOI] [PubMed] [Google Scholar]
- Egan Michael F., Kojima Masami, Callicott Joseph H., Goldberg Terry E., Kolachana Bhaskar S., Bertolino Alessandro, Zaitsev Eugene, Gold Bert, Goldman David, Dean Michael. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257–269. doi: 10.1016/s0092-8674(03)00035-7. [DOI] [PubMed] [Google Scholar]
- Engleman H. M., Douglas N. J. Sleep. 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome. Thorax. 2004 Jul;59(7):618–622. doi: 10.1136/thx.2003.015867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujihara Hiroaki, Sei Hiroyoshi, Morita Yusuke, Ueta Yoichi, Morita Kyoji. Short-term sleep disturbance enhances brain-derived neurotrophic factor gene expression in rat hippocampus by acting as internal stressor. J Mol Neurosci. 2003;21(3):223–232. doi: 10.1385/jmn:21:3:223. [DOI] [PubMed] [Google Scholar]
- Fujimura Hironobu, Altar C. Anthony, Chen Ruoyan, Nakamura Takashi, Nakahashi Takeshi, Kambayashi Jun-ichi, Sun Bing, Tandon Narendra N. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost. 2002 Apr;87(4):728–734. [PubMed] [Google Scholar]
- Hairston Ilana S., Peyron Christelle, Denning Daniel P., Ruby Norman F., Flores Judith, Sapolsky Robert M., Heller H. Craig, O'Hara Bruce F. Sleep deprivation effects on growth factor expression in neonatal rats: a potential role for BDNF in the mediation of delta power. J Neurophysiol. 2003 Dec 10;91(4):1586–1595. doi: 10.1152/jn.00894.2003. [DOI] [PubMed] [Google Scholar]
- Henke K. G., Grady J. J., Kuna S. T. Effect of nasal continuous positive airway pressure on neuropsychological function in sleep apnea-hypopnea syndrome. A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2001 Mar;163(4):911–917. doi: 10.1164/ajrccm.163.4.9910025. [DOI] [PubMed] [Google Scholar]
- Hobson J. Allan, Pace-Schott Edward F. The cognitive neuroscience of sleep: neuronal systems, consciousness and learning. Nat Rev Neurosci. 2002 Sep;3(9):679–693. doi: 10.1038/nrn915. [DOI] [PubMed] [Google Scholar]
- Hui David S., Ko Fanny W., Fok Joan P., Chan Michael C., Li Thomas S., Tomlinson Brian, Cheng Gregory. The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome. Chest. 2004 May;125(5):1768–1775. doi: 10.1378/chest.125.5.1768. [DOI] [PubMed] [Google Scholar]
- Karege Félicien, Perret Guillaume, Bondolfi Guido, Schwald Michèle, Bertschy Gilles, Aubry Jean-Michel. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002 Mar 15;109(2):143–148. doi: 10.1016/s0165-1781(02)00005-7. [DOI] [PubMed] [Google Scholar]
- Karege Félicien, Schwald Michèle, Cisse Mbaye. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett. 2002 Aug 16;328(3):261–264. doi: 10.1016/s0304-3940(02)00529-3. [DOI] [PubMed] [Google Scholar]
- Kishino Akiyoshi, Nakayama Chikao. Enhancement of BDNF and activated-ERK immunoreactivity in spinal motor neurons after peripheral administration of BDNF. Brain Res. 2003 Feb 21;964(1):56–66. doi: 10.1016/s0006-8993(02)04066-0. [DOI] [PubMed] [Google Scholar]
- Kohara K., Kitamura A., Morishima M., Tsumoto T. Activity-dependent transfer of brain-derived neurotrophic factor to postsynaptic neurons. Science. 2001 Mar 23;291(5512):2419–2423. doi: 10.1126/science.1057415. [DOI] [PubMed] [Google Scholar]
- Lommatzsch M., Braun A., Mannsfeldt A., Botchkarev V. A., Botchkareva N. V., Paus R., Fischer A., Lewin G. R., Renz H. Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions. Am J Pathol. 1999 Oct;155(4):1183–1193. doi: 10.1016/S0002-9440(10)65221-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lommatzsch Marek, Schloetcke Katharina, Klotz Jens, Schuhbaeck Katharina, Zingler Doerte, Zingler Christiana, Schulte-Herbrüggen Olaf, Gill Hartmut, Schuff-Werner Peter, Virchow Johann Christian. Brain-derived neurotrophic factor in platelets and airflow limitation in asthma. Am J Respir Crit Care Med. 2004 Oct 29;171(2):115–120. doi: 10.1164/rccm.200406-758OC. [DOI] [PubMed] [Google Scholar]
- Lommatzsch Marek, Zingler Doerte, Schuhbaeck Katharina, Schloetcke Katharina, Zingler Christiana, Schuff-Werner Peter, Virchow Johann Christian. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging. 2005 Jan;26(1):115–123. doi: 10.1016/j.neurobiolaging.2004.03.002. [DOI] [PubMed] [Google Scholar]
- Monteggia Lisa M., Barrot Michel, Powell Craig M., Berton Olivier, Galanis Victor, Gemelli Terry, Meuth Sven, Nagy Andreas, Greene Robert W., Nestler Eric J. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A. 2004 Jul 12;101(29):10827–10832. doi: 10.1073/pnas.0402141101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pan W., Banks W. A., Fasold M. B., Bluth J., Kastin A. J. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998 Dec;37(12):1553–1561. doi: 10.1016/s0028-3908(98)00141-5. [DOI] [PubMed] [Google Scholar]
- Radka S. F., Holst P. A., Fritsche M., Altar C. A. Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay. Brain Res. 1996 Feb 12;709(1):122–301. doi: 10.1016/0006-8993(95)01321-0. [DOI] [PubMed] [Google Scholar]
- Schlosshan D., Elliott M. W. Sleep . 3: Clinical presentation and diagnosis of the obstructive sleep apnoea hypopnoea syndrome. Thorax. 2004 Apr;59(4):347–352. doi: 10.1136/thx.2003.007179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherwood N. T., Lo D. C. Long-term enhancement of central synaptic transmission by chronic brain-derived neurotrophic factor treatment. J Neurosci. 1999 Aug 15;19(16):7025–7036. doi: 10.1523/JNEUROSCI.19-16-07025.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Udwadia Zarir F., Doshi Amita V., Lonkar Sharmila G., Singh Chandrajeet I. Prevalence of sleep-disordered breathing and sleep apnea in middle-aged urban Indian men. Am J Respir Crit Care Med. 2003 Nov 6;169(2):168–173. doi: 10.1164/rccm.200302-265OC. [DOI] [PubMed] [Google Scholar]
- Yamada Kiyofumi, Mizuno Makoto, Nabeshima Toshitaka. Role for brain-derived neurotrophic factor in learning and memory. Life Sci. 2002 Jan 4;70(7):735–744. doi: 10.1016/s0024-3205(01)01461-8. [DOI] [PubMed] [Google Scholar]
- Young T., Palta M., Dempsey J., Skatrud J., Weber S., Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230–1235. doi: 10.1056/NEJM199304293281704. [DOI] [PubMed] [Google Scholar]
