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

ELEFANTE 19

CAVALLO 29

GORILLA 70

IN BASE A REGISTRAZIONI EEG:

ASINO 13

RATTO 50

GATTO 60

CONIGLIO 60

CENNI STORICICENNI STORICICENNI 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 PARAMETRI FISIOLOGICI PER LA DEFINIZIONE DEL SONNODEL SONNO

CM S D

R

IPNOGRAMMAIPNOGRAMMA

Pre - sleep - WPre - sleep - W SWSSWS REM - sleepREM - sleep

Post - sleep - WPost - sleep - W

ACTIVATION

High DEACTIVATION

Low DEACTIVATION

ACTIVATION

High DEACTIVATION

Low DEACTIVATION

BRAUN et al; Brain (1997)

Sleep Academic Award 12

Dijk and Edgar, 1999, Lung Biology in Health and Disease, vol.133

 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-complexOnde deltaSt. NREM differenti

VARIAZIONI DEL CICLO SONNO-VEGLIA

Arousal

SleepSleep No sleepNo sleep

acuteacutesleepsleep

deprivationdeprivation

Cortisol Cortisol (µg/dl)(µg/dl)

Thyrotropin Thyrotropin (µU/ml)(µU/ml)

ProlactinProlactin(ng/ml)(ng/ml)

Growth Growth HormoneHormone

(µg/L)(µg/L)

Clock TimeClock Time

10 14 18 22 02 06 10 10 14 18 22 02 06 10

10 14 18 22 02 06 10 10 14 18 22 02 06 10

10 14 18 22 02 06 10 10 14 18 22 02 06 10

0

5

10

15

20

25

0

5

10

15

20

0

5

10

15

20

01

02

03

04

05

0

5

10

15

20

25

0

5

10

15

20

0

5

10

15

20

01

02

03

04

05

10 14 18 22 02 06 10 10 14 18 22 02 06 10

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 USSelf-reported Sleep and the Prevalence of Obesity in the US

55

66

77

88

99

19501950 19601960 19701970 19801980 19901990 20002000 201020100%0%

5%5%

10%10%

15%15%

25%25%

Sle

ep

(h

ou

rs)

Sle

ep

(h

ou

rs)

Ob

esi

ty p

reva

len

ceO

be

sity

pre

vale

nce20%20%

Sleep (adult)Sleep (adult)ObesityObesity

Continuous glucose infusion (5g/kg/24h)

LEPTIN(ng/ml)

1.5

2.0

2.5

3.0

3.5

9 11 13 15 17 19 21CLOCK TIME

GHRELIN(ng/ml)

2.2

2.8

3.4

AFTER 2 DAYS OF10-H BEDTIMES

AFTER 2 DAYS OF4-H BEDTIMES

p level % change9-21 leptin levels (ng/ml) 2.6 ± 0.5 2.1 ± 0.4 0.041 -19%12-21 ghrelin levels (ng/ml) 2.6 ± 0.2 3.3 ± 0.2 0.038 +24%

DAYTIME LEPTIN AND GHRELIN LEVELS

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

Lange et al (2003) Psychosomatic Medicine 65: 831-835

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

response to influenza vaccination is impaired in individuals with chronic partial sleep restriction

Spiegel et al (2002) JAMA 288: 1471-1472

Sleep restriction to 4 hours/night, for 4 days before and 2 days after vaccination, impairs immune response to vaccination

Nofzinger et al. Am J Psychiatry 2004;161:2126-2128

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)

SLEEP DEBT

Reduced cortical cholinergic activity

Frontal Lobe dysfunctions

Harrison & Horne, 2000; Boonstra et al., 2007

Increased Adenosine

One single night of sleep loss significantly reduces prefrontal metabolic activity

PET studies

Thomas et al., J Sleep Res, 2007, 9: 335-352

J Clin Sleep Med, 2007