La fisiologia del
sonno
Luigi Ferini-Strambi
Centro di Medicina del
Sonno
Università Vita-Salute San
Raffaele, Milano
IL SONNO NEGLI ANIMALI
(DURATA IN % DI 24 ORE)
IN BASE
ALL’OSSERVAZIONE:
MUCCA
3
IN BASE A
REGISTRAZIONI EEG:
ASINO
13
ELEFANTE 19
RATTO
50
CAVALLO
29
GATTO
60
GORILLA
70
CONIGLIO 60
CENNI STORICI
 “The electric currents of the brain” Caton, 1875
 “waking and sleeping states” Berger, 1930
 “Cerebral states during sleep as studied by humans brain
potentials” Loomis, 1937
 “electro-oculography” Aserinsky & Kleitman, 1953
 “The REM sleep”; Dement & Kleitman, 1957
 “electromyographic activity is suppressed in REM sleep”
Jouvet, 1959
 Video-EEG / PSG ‘70
Organizzazione gerarchica delle strutture
responsabili del sonno
( L. Parmeggiani )
Veglia
NREM
REM
corteccia
ipotalamo
tronco
ipotalamo
tronco
corteccia
tronco
corteccia
ipotalamo
PARAMETRI FISIOLOGICI PER LA DEFINIZIONE
DEL SONNO
C
MS D
R
IPNOGRAMMA
Pre - sleep - W
SWS
REM - sleep
Post - sleep - W
ACTIVATION
ACTIVATION
High
High DEACTIVATION
DEACTIVATION
Low
Low DEACTIVATION
DEACTIVATION
BRAUN et al; Brain (1997)
Sleep Academic Award
12
Dijk and Edgar, 1999, Lung Biology in Health and Disease, vol.133
VARIAZIONI DEL CICLO SONNO-VEGLIA
Neonato /
Bambino
Adulto
% REM / NREM
50 / 50
20 / 80
Periodicità stadi di
sonno
50-60’
90-100’
Esordio sonno
REM
NREM
Organizzazione
temporale stadi di
sonno
I cicli REM/NREM
egualmente distribuiti
durante il sonno
I cicli NREM 3-4 nel
primo terzo della notte;
REM nell’ultimo terzo
Maturazione
pattern EEG
1 solo stadio NREM
> stadi indeterminati
K-complex
Onde delta
St. NREM differenti
Arousal
Sleep
No sleep
20
20
15
15
Cortisol
10
10
(µg/dl)
5
5
0
10
05
14
18
22
02
06
10
0
10
05
04
04
Thyrotropin
03
03
(µU/ml)
02
02
01
10
01
10
Prolactin
(ng/ml)
(µg/L)
18
22
02
06
10
25
25
20
20
15
15
10
10
5
5
0
10
Growth
Hormone
14
14
18
22
02
06
10
0
10
20
20
15
15
10
10
5
5
0
10
14
18
22
02
06
10
0
10
14
18
22
02
06
10
14
18
22
02
06
10
14
18
22
02
06
10
14
18
22
02
06
10
Clock Time
acute
sleep
deprivation
Cortisol rhythm
Impact of sleep debt on metabolic
and endocrine function
Spiegel K, et al. The Lancet 1999, 354:1435–1439.
• Intolleranza glucidica
• ↓Clearance glucosio
40%
• ↓Risposta insulinica al
glucosio 30%
• Recupero sonno
normalizza i valori
Grasso è bello ???
Self-reported Sleep and the Prevalence of Obesity in the US
25%
20%
8
15%
7
10%
6
Sleep (adult)
Obesity
5%
0%
5
1950 1960 1970 1980 1990 2000 2010
Obesity prevalence
Sleep (hours)
9
DAYTIME LEPTIN AND GHRELIN LEVELS
Continuous glucose infusion (5g/kg/24h)
3.5
LEPTIN
(ng/ml)
3.0
2.5
2.0
1.5
AFTER 2 DAYS OF
10-H BEDTIMES
3.4
GHRELIN
(ng/ml)
AFTER 2 DAYS OF
4-H BEDTIMES
2.8
2.2
9
11
13 15 17
CLOCK TIME
9-21 leptin levels (ng/ml)
2.6 ± 0.5
12-21 ghrelin levels (ng/ml) 2.6 ± 0.2
19
2.1 ± 0.4
3.3 ± 0.2
21
p level
0.041
0.038
% change
-19%
+24%
PRIVAZIONE DI SONNO
• Diminuisce l’attività delle cellule “natural
killers” nell’uomo
Moldofsky, 1989
• Impedisce nel topo messo a contatto con un
virus influenzale di sviluppare “memoria
immunitaria”
Brown et al, 1989
sleep loss impairs the human antibody response to
hepatisis A vaccination
total loss of sleep in the night following vaccination
impairs immune response 28 days later
Lange et al (2003) Psychosomatic Medicine 65: 831-835
response to influenza vaccination is impaired
in individuals with chronic partial sleep restriction
Sleep restriction to 4 hours/night, for 4 days before and 2 days after vaccination,
impairs immune response to vaccination
Spiegel et al (2002) JAMA 288: 1471-1472
Brain Structures That Did Not Show Decreased Metabolic Rate
From Waking to Sleep States in Patients With Insomnia (A) and
Brain Structures Where Relative Metabolism While Awake Was
Significantly Higher in Healthy Subjects Than in Patients With
Insomnia (B)
Nofzinger et al. Am J Psychiatry 2004;161:2126-2128
SLEEP DEBT
Reduced cortical
cholinergic activity
Increased Adenosine
Frontal Lobe
dysfunctions
Harrison & Horne, 2000; Boonstra et al., 2007
PET studies
One single night of sleep loss
significantly reduces prefrontal
metabolic activity
Thomas et al., J Sleep Res, 2007, 9: 335-352
J Clin Sleep Med, 2007