Table 1
Medial prefrontal cortex microdialysis results.
| Amino acid | Phase | Median (μM) | 25%–75% IQR (μM) | N | G(df) | p |
|---|---|---|---|---|---|---|
| Asn | Wash-out | 1.28 | 0.40–2.24 | 10 | 20.3 (4) | <0.001 |
| Baseline Light | 0.11 | 0.08–0.19 | 11 | |||
| Baseline Dark | 0.15 | 0.08–0.20 | 11 | |||
| SD | 0.11 | 0.10–0.20 | 11 | |||
| Recovery | 0.13 | 0.09–0.20 | 11 | |||
| Sleep deprivation vs. Baseline Light: t = 42.5; p = 0.40 | ||||||
| Recovery vs. Baseline Dark: t = 31.0; p = 0.86 | ||||||
| Baseline Light vs. Baseline Dark: t = 40.0; p = 0.53 | ||||||
| Asp | Wash-out | 0.06 | 0.05–0.08 | 10 | 20.3 (4) | <0.001 |
| Baseline Light | 0.05 | 0.04–0.06 | 11 | |||
| Baseline Dark | 0.04 | 0.04–0.06 | 11 | |||
| SD | 0.05 | 0.04–0.06 | 11 | |||
| Recovery | 0.05 | 0.03–0.06 | 11 | |||
| Sleep deprivation vs. Baseline Light: t = 42.5; p = 0.40 | ||||||
| Recovery vs. Baseline Dark: t = 31.0; p = 0.86 | ||||||
| Baseline Light vs. Baseline Dark: t = 40.0; p = 0.53 | ||||||
| GABA | Wash-out | 0.09 | 0.07–0.13 | 10 | 3.44 (4) | 0.49 |
| Baseline Light | 0.09 | 0.06–0.13 | 11 | |||
| Baseline Dark | 0.10 | 0.05–0.11 | 11 | |||
| SD | 0.08 | 0.06–0.12 | 11 | |||
| Recovery | 0.09 | 0.06–0.11 | 11 | |||
| Gln | Wash-out | 5.40 | 0.16–11.8 | 10 | 10.67 (4) | 0.031 |
| Baseline Light | 0.03 | 0.03–0.09 | 11 | |||
| Baseline Dark | 0.04 | 0.02–0.05 | 11 | |||
| SD | 0.07 | 0.02–0.09 | 11 | |||
| Recovery | 0.07 | 0.05–0.12 | 11 | |||
| Sleep deprivation vs. Baseline Light: t = 31.0; p = 0.72 | ||||||
| Recovery vs. Baseline Dark: t = 62.0; p = 0.010 | ||||||
| Baseline Light vs. Baseline Dark: t = 23.0; p = 0.65 | ||||||
| Glu | Wash-out | 0.10 | 0.53–1.44 | 10 | 15.2 (4) | 0.004 |
| Baseline Light | 0.16 | 0.09–0.19 | 11 | |||
| Baseline Dark | 0.31 | 0.25–0.34 | 11 | |||
| SD | 0.27 | 0.26–0.39 | 11 | |||
| Recovery | 0.34 | 0.20–0.50 | 11 | |||
| Sleep deprivation vs. Baseline Light: t = 61.0; p = 0.013 | ||||||
| Recovery vs. Baseline Dark: t = 46.0; p = 0.25 | ||||||
| Baseline Light vs. Baseline Dark: t = 66.0; p = 0.003 | ||||||
| Gly | Wash-out | 0.43 | 0.26–0.78 | 10 | 19.0 (4) | 0.001 |
| Baseline Light | 0.11 | 0.08–0.15 | 11 | |||
| Baseline Dark | 0.08 | 0.06–0.12 | 11 | |||
| SD | 0.08 | 0.06–0.11 | 11 | |||
| Recovery | 0.08 | 0.06–0.15 | 11 | |||
| Sleep deprivation vs. Baseline Light: t = 3.0; p = 0.23 | ||||||
| Recovery vs. Baseline Dark: t = 4.0; p = 0.55 | ||||||
| Baseline Light vs. Baseline Dark: t = 4.0; p = 0.55 | ||||||
| Hist | Wash-out | 0.04 | 0.03–0.05 | 10 | 3.1 (4) | 0.54 |
| Baseline Light | 0.03 | 0.03–0.05 | 10 | |||
| Baseline Dark | 0.04 | 0.03–0.05 | 11 | |||
| SD | 0.03 | 0.03–0.05 | 11 | |||
| Recovery | 0.03 | 0.03–0.04 | 11 | |||
| Pro | Wash-out | 0.35 | 0.07–0.63 | 10 | 5.3 (4) | 0.26 |
| Baseline Light | 0.09 | 0.06–0.26 | 10 | |||
| Baseline Dark | 0.10 | 0.06–0.36 | 10 | |||
| SD | 0.12 | 0.07–0.30 | 11 | |||
| Recovery | 0.11 | 0.07–0.26 | 11 | |||
| Tau | Wash-out | 0.61 | 0.55–0.85 | 10 | 3.8 (4) | 0.44 |
| Baseline Light | 0.88 | 0.51–1.14 | 11 | |||
| Baseline Dark | 0.85 | 0.60–1.14 | 11 | |||
| SD | 1.10 | 0.47–1.23 | 11 | |||
| Recovery | 0.60 | 0.35–0.97 | 11 | |||
[i] Asn = Asparagine, Asp = Aspartate, GABA = Gamma-AminoButyric Acid, Gln =Glutamine, Glu = Glutamate, Gly = Glycine, Hist = Histamine, Pro = Proline, Tau = Taurine, SD = Sleep Deprivation, IQR = InterQuartile Range, N = number of rats, G = the test statistic of the Friedman’s test, df = degrees of freedom, p = p-value of the Friedman’s test.
Figure 1
Flow scheme of retrieved and included references.
TiAb – Title-Abstract; μD = microdialysis.
Table 2
Studies of microdialysate histamine and amino acid levels during naturally occurring sleep.
| Study_ID | Species | Brain Area | Summary |
|---|---|---|---|
| Azuma_1996 [27] | Rats | mPOA | Glu was higher during wake (2.04 ± 0.22μM) and wake-to NREM transitions (2.22 ± 0.63μM) than during NREM sleep (1.56 ± 0.27μM) or NREM-to wake transitions (1.26 ± 0.28μM). |
| Chu_2004 [28] | Rats | Frontal cortex | Hist release was 3.8 times higher during wake episodes (0.19 ± 0.01 pmol/20 min) than during sleep episodes (0.05 ± 0.002 pmol/20 min). |
| Gronli_2007 [26] | Rats | Hippocampus | GABA levels did not show state-dependent variations (wake: 1600.5 ± 393.4 fmol/sample; SWS: 1530.5 ± 408.4 fmol/24μl sample; REM: 1503.0 ± 388.1 fmol/sample). |
| Hasegawa_2000 [29] | Rats | PRN | Gly levels (in the low μM range, exact values not provided) were higher during REM than during NREM and wake. Glu and Gln levels (in the low μM range, exact values not provided) were not state-dependent. |
| John_2008 [22] | Rats | TMN | No significant differences in hypothalamic Glu levels were observed between REM (2.5 ± 0.17 pmol/10μl sample), SWS (2.4 ± 0.06 pmol/sample) and W (2.5 ± 0.17; 2.4 ± 0.06 and 2.3 ± 0.12 pmol/sample). |
| Kekesi_1997 [23] | Cats | VPL | Asp, Asn, Glu, Gly, Tau and GABA were significantly elevated during SWS (exact values not provided) compared to the awake baseline (Asp: 1.7 ± 0.03 μM; Asn: 1.5 ± 2.0 μM; Glu: 6.6 ± 0.3 μM; Gly: 8.7 ± 0.6 μM; Tau: 17.8 ± 0.7 μM; GABA: 0.7 ± 0.2 μM). Gln did not show state-dependent variations (61.3 ± 3.4 μM at baseline wake). |
| Kodama_1998 [30] | Cats | PIA, NMC, NPM | Glu levels during SWS were taken as reference (NMC: 217.5 ± 21.9; PIA: 164.3 ± 18.1; NPM: 239.6 ± 23.5 fmol/min sample). During REMS, Glu in NMC increased to 111% of SWS, significantly different from Glu during W (98% of SWS). In the other areas no such difference was observed. |
| Lena_2005 [31] | Rats | mPFC, Nacc | In the NAcc, Glu was lower during SWS (5.69 × 10–7 ± 1.53 M) and REM (5.57 × 10–7 ± 1.47 M) than during wake (9.28 × 10–7 ± 2.89 M). ANOVA indicated a difference in Asp concentrations (SWS: 2.24 × 10–7 ± 1.3 M; REM: 2.25 × 10–7 ± 1.21 M; wake: 5.1 × 10–7 ± 2.3 M), but post-hoc analyses were negative. No state-dependent changes in Asp and Glu levels were observed in the mPFC (wake Asp: 2.51 × 10–7 ± 0.18 M; Glu: 16.2 × 10–7 ± 2.9 M; SWS Asp: 2.79 × 10–7 ± 0.58 M; Glu: 16.1 × 10–7 ± 6 2.5 M; REM Asp: 2.33 × 10–7 ± 0.28 M; Glu: 15.9 × 10–7 ± 2.6 M). |
| LopezRodriguez_2007 [32] | Rats | Orbitofrontal Cortex | Glu levels (range: 0.17–5.28 μM) were higher during REM (134 ± 14% of overall mean) than during wake (106 ± 5%), and lower during SWS (87 ± 5%) than during wake. |
| Nitz_1997a [33] | Cats | Dorsal raphe | GABA was higher during REM sleep (0.072 ± 0.003 pmol/μL) than during SWS (0.049 ± 0.007 pmol/μL) and wake (0.042 ± 0.005 pmol/μL). Glu (wake: 35.84 ± 2.55 pmol/μL; SWS: 36.42 ± 4.57 pmol/μL; REM: 33.98 ± 2.03 pmol/μL) and Gly (wake: 32.30 ± 4.29 pmol/μL; SWS: 34.05 ± 4.80 pmol/μL; REM: 33.89 ± 4.11 pmol/μL) levels were not state-dependent. |
| Nitz_1997b [34] | Cats | Locus Coeruleus | GABA was higher during REM sleep (1.91 ± 0.2 fmol/μL) than during SWS (1.58 ± 0.2 fmol/μL) and wake (1.2 ± 0.3 fmol/μL). Glu (wake: 0.88 ± 0.20 pmol/μL; SWS: 0.90 ± 0.20 pmol/μL; REM: 0.95 ± 0.25 pmol/μL) and Gly (wake: 0.54 ± 0.16 pmol/μL; SWS: 0.45 ± 0.14 pmol/μL; REM: 0.48 ± 0.13 pmol/μL) levels were not state-dependent. |
| Strecker_2002 [35] | Cats | POAH | Hist was highest during wakefulness (1.155 ± 0.225 pg/μl), lower during SWS (0.395 ± 0.081 pg/μl) and lowest during REM-sleep (0.245 ± 0.032 pg/μl). Note that after conversion (wake: 0.312 ± 0.061 pmol/20 min; REM 0.066 ± 0.009; SWS 0.107 ± 0.022), these values are quite comparable to those of Chu [28]. |
| Vanini_2011 [36] | Cats | PRN | GABA decreased during REM (0.268 ± 0.050 pmol/10μL) versus both wake (0.466 ± 0.046 pmol/10μL) and SWS (0.365 ± 0.046 pmol/10μL), which did not differ from each other. |
| Vanini_2012 [37] | Cats | sCTX, BF | In the BF, GABA levels were higher during SWS (1.042 pmol/10μL) than during REM (0.836 pmol/10μL) and wake (0.977 pmol/10μL). In the somatosensory cortex, GABA levels were higher during SWS (1.275 pmol/10μL) than during wake (1.15 pmol/10μL) and REM (0.932 pmol/10μL). |
| Watson_2011 [38] | Rats | PRN | Concentrations of both Glu and GABA were higher during wake (Glu: 1.948 ± 0.018 μM; GABA: 0.428 ± 0.003 μM) than during NREM (Glu 85.8% of wake; GABA 89.0%) and REM (Glu 83.6% of wake; GABA 81.3%). Asp (0.522 ± 0.003 μM during wake), Tau (7.442 ± 0.055 μM during wake) and Gly (4.942 ± 0.046 μM during wake) did not show state-dependent changes. |
[i] ANOVA = ANalysis Of VAriance; BF = Basal Forebrain; mPFC = Medial PreFrontal Cortex; NAcc = Nucleus Accumbens; NMC = Nucleus MagnoCellularis; NPM = Nucleus ParaMedianus; PIA = Pontine Inhibitory Area; POAH = Preoptic/Anterior Hypothalamic Area; NREM = Non-REM; PRN = Pontine Reticular Formation; sCTX = somatosensory Cortex; SWS = Slow Wave Sleep; TMN = TuberoMammillary Nucleus; VPL = VentroPosteroLateral thalamic nuclei.
Table 3
Sleep deprivation studies.
| Study_ID | Species | Brain Area | SD method | Summary |
|---|---|---|---|---|
| John_2008 [22] | Rats | hypothalamus, cortex | Gentle Handling | Sleep deprivation had no significant effect on hypothalamic Glu (2.8 ± 0.02 vs. 2.5 ± 0.04 pmol/sample), but it increased cortical Glu (0.72 ± 0.14 μM vs. 0.35 ± 0.05 μM). |
| Strecker_2002 [35] | Cats | POAH | Gentle Handling | Hist levels during sleep deprivation (no exact values given) were comparable with those during wakefulness (1.155 ± 0.225 pg/μl; after conversion: 0.312 ± 0.061 pmol/20 min). |
| Vanini_2012 [37] | Cats | CTX, BF | na | Cortical GABA increased during extended wakefulness, BF GABA levels did not (no exact values given). |
| Xie_2015 [39] | Rats | Hippocampus | Platform-water tank (PSD) | Glu and GABA were higher at the end of 24h of paradoxical sleep deprivation (Glu: 500 ± 138 μmol/L; GABA: no exact values given) than during baseline (Glu: 0.74 ± 0.07 μmol/L; GABA: 0.27 ± 0.03 μmol/L). Of note, microdialysis flow was decreased during the SD period. Increased recovery due to decreased flow rate may have confounded these findings. |
| Zant_2012 [40] | Rats | Basal Forebrain | Gentle Handling | Sleep deprivation increased Hist levels (in the nM range, no exact values given). |
[i] BF = Basal Forebrain; CTX = Cortex; na = information not available; POAH = Preoptic/Anterior Hypothalamic Area.