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| Content Provider | Springer Nature Link |
|---|---|
| Author | Savolainen, Heli Meerlo, Peter Elsinga, Philip H. Windhorst, Albert D. Dierckx, Rudi A.J.O. Colabufo, Nicola A. van Waarde, Aren Luurtsema, Gert |
| Copyright Year | 2016 |
| Abstract | The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from harmful compounds. P-glycoprotein (P-gp) is one of the major efflux transporters at the BBB. In the present study, we assessed whether (1) P-gp function in the brain is constant or fluctuates across the day and (2) if it is affected by sleep deprivation. Four groups of rats were PET scanned with a radiolabeled P-gp substrate [$^{18}$F]MC225, each at a different moment of the 12-h light-dark cycle to study diurnal variations: early sleep phase (ZT3), late sleep phase (ZT9), early active phase (ZT15), and late active phase (ZT21). In two additional groups, controls were allowed to sleep normally while experimental animals were sleep-deprived for 10 h in a slowly rotating drum during the sleep phase. Kinetic modeling with a one-tissue compartment model fit resulted for all brain regions in 1.2–1.8-fold higher distribution volumes (V $_{ T }$) at ZT15 than at other time points. V $_{ T }$-values at ZT3, ZT9, and ZT21 were not significantly different from each other. Regional tracer distribution volumes in controls and sleep-deprived animals were also not significantly different. Our results indicate that P-gp function in rats displays a daily rhythm with reduced function at the beginning of the active phase. This rhythm is not dependent on sleep since acute sleep deprivation had no effect. Knowing the diurnal variation of P-gp function could be important for the design of PET studies and for choosing the correct administration time for P-gp-dependent drugs. |
| Starting Page | 1524 |
| Ending Page | 1531 |
| Page Count | 8 |
| File Format | |
| ISSN | 12341234 |
| Journal | The AAPS Journal |
| Volume Number | 18 |
| Issue Number | 6 |
| e-ISSN | 15507416 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2016-09-06 |
| Publisher Institution | American Association of Pharmaceutical Scientists |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | circadian rhythm efflux transporter [$^{18}$F]MC225 pharmacokinetic modeling sleep deprivation Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy |
| Content Type | Text |
| Resource Type | Article |
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