Post on 15-Feb-2019
TEST GLOBALE DEI NEUROTRASMETTITORI
PSICOSOMATICI
Evasio Pasini (Cardiologo)
COSA C’ENTRA LA CARDIOLOGIA CON
LA PNEI?
3
The Neuro, Endo, and Immune systems are in constant conversaFon
and regulate global metabolism and cell life
! … ?
3
N E I
The Neuro-‐Endo-‐Immune (NEI) System is Represented By:
Cytokines
Hormones
NeurotransmiNers
5
The NEI System
Understanding the Cross talk between the 3 key systems
Regional SNS Control of Immunity Consists of Two Components
1. Neuronal component (Sympathe=c Nerves)
– Through innerva=on of immune organs and release of NE and other neurotransmiBers or pep=des
2. Hormonal component (HPA-‐axis) – Regulates immunity (inflamma=on) systemically – Through release of Epi and cor=sol from the adrenal
glands
The Brain Monitors and Regulates Immune Responses (A)
• Signaling between the immune system and the CNS is mediated by: – Sympathe=c nervous system (SNS)
– Parasympathic nervous system (PNS)
• Vagus nerve
Sternberg, E.M. (2006). Neural regulation of innate immunity: A coordinated nonspecific host response to pathogens. Nature Reviews, 6, 318-328.
8
• Inflamma&on influences Hormones
• Hormones influences Inflamma&on
Inflammatory triggers: • Bacteria • Parasites • Viruses • Food proteins • Environmental toxins • Psychosocial stress
Sternberg, E.M. (2006). Nature Reviews 6:318-‐328.
Neuropep=des in Inflamma=on
• S=mulatory – Cor=cotrophin releasing hormone (CRH) – Neuropep=de Y (NPY) – Substance P – Calcitonin gene-‐related pep=de (CGRP)
• Inhibitory – Vasoac=ve intes=nal pep=de (VIP) – Opiods (methionine-‐eukephaline) – α-‐Melanocyte s=mulatory hormone (α-‐MSH)
ENDOCRINE PLAYERS IN INFLAMMATION
• Adrenal Hormones (cor=costeroids)
• Sex Hormones (Estrogens, Progesterone)
• Thyroid Hormones
InflammaFon can affect neurotransmiNer levels & behavior
↓ serotonin
↑ glutamate
↑ quinolinic acid1
1Halperin & Heyes, 1992
Excitotoxicity & apoptosis
Do these symptoms look familiar?
12
Brain Fog
Insomnia Cognitive Issues
Anxiety Weight Gain
Fatigue Depression
Poor Psychomotor Performance
Irritability
Sensory Hyperarousal
Chronic inflamma&on can result in these and other neuro/endo/metabolic
symptoms
12
ESEMPIO (Intake Alimentare) RETE SEGNALI TRA ORGANI Cervello-‐IntesFno-‐Tessuto Adiposo-‐Muscolo-‐Pancreas
BRAIN AgRP Catecholam.
MCH Cor&sol NPY Neurotrasm. Α-‐MSH Releas. Factors Orexin CART
Neurotensin
GastrointesFne Adipose Tissue Muscle Pancreas
Gherlin GLP1 Adiponec&n AAs Bombesin Obesta&n Lep&n Amylin CCK Resis&n Glucagon GIP TNF-‐α Insulin PYY Polipe&des
COME GLI ORNOMI E LE CITOCHINE INFLUENZANO
IL METABOLISMO/FUNZIONE GENERALE
E MUSCOLARE?
16
MUSCLE
Protein Breakdown Protein syntesis
AA AA Energy
Catabolic Stimuli
• Cortisol • Catecholamines • Glucagone • Cytokines • Others
Anabolic S&muli
• Insulin • IGF-‐alfa • Others
AA Release
Blood pool Of AA
Glucose (via gluconeogenesis)
Cellular Protein Syntesis
Cellular Energy Production
NORMAL
17
MUSCLE
Protein Breakdown
Protein syntesis
AA Release
Blood pool Of AA
Glucose (via gluconeogenesis)
Cellular Protein Syntesis
Cellular Energy Production
Catabolic Stimuli
• Cortisol • Catecholamines • Glucagone • Cytokines • Others
Anabolic Stimuli
• Insulin • IGF • Others
Ipercatabolic Sindrom Insulin Resistence
EffeBo NEI sull’ANZIANO
Evidenze Clinico/Sperimentali
19
Young Control (water)
Elder Control. Large space between myofibres are seen commonly (arrows).
Muscle
20
Groups Treatment Sarcomere
Area
Mithocondria
Area
N° Mitocondia
Surfece Unit
1 Young
0,79
± 0,13
0,45
±0.19
12.38
± 5.77
2 Elder
0,57
± 0,2
0,15
±0.05
4.5
± 2.9
Statistic
P<0.05
1 vs 2
1 vs 2
1 vs 2
Skeletal Muscle: Morphometric Pameters
Total area examine = 115,000µ2 in each group .
21
DNA Mitocondriale Totale
012345678910
Giovani Anziani
22
PGC-‐1Alfa (gene che regola la mitocondriogenesi)
0
5
10
15
20
25
Giovani Anziani
23
Anziano controllo 20x
Luce polarizzata
(fibre rosse = fibrosi))) oltre alla fibrosi si osserva una forte disorganizzazione delle fibre collagene.
Giovane controllo 20x
Luce polarizzata
(fibre gialle = collagene costitutivo) Non si osserva fibrosi disorganizzazione del collagene
Sirius Red: valutazione fibrosi muscolo scheletrico Luce polarizzata
Luce polarizzata
EffeBo NEI sullo Scompenso Cardiaco
Evidenze Clinico/Sperimentali
25
Is Nutri&onal Intake Adequate in CHF Pa&ents?
Aquilani, Pasini et al: J Am Coll Cardiol 42(7) 1218-‐1223-‐2003
• 57 pz non obesi anziani (NYHA II-‐III) + 49 controlli • BMI>25 • Valuta= per 7 gg:
– Introduzione quan=/qualita=va di cibo – Res=ng e Total Energy Expenditure (REE e TEE) mediante calorimetria indireBa
– Bilancio azotato (valutazione demolizione AA) – Quadro ormonale (bilancia ana/catabolica)
26
Is Nutri&onal Intake Adequate in CHF Pa&ents? Consumo EnergeFco
Resting Energy Expenditure
0
250
500
750
1000
kcal/m
2
Control CHF
*
Total Energy Expenditure
0
1000
2000
Control CHF
*
kcal/m
2
* p<0.01
Figure 1
27
Is Nutri&onal Intake Adequate in CHF Pa&ents? Bilancio Calorico
Calorie Balance
-300
-200
-100
0
100
200
300
Control CHF*
kcal
/day
* p<0.01
Figure 2
28
Is Nutri&onal Intake Adequate in CHF Pa&ents? Bilancio Azotato
Nitrogen Balance
-3
-2
-1
0
1
2
3
Control CHF*
g/d
ay
* p<0.01
Figure 3
29
Is Nutri&onal Intake Adequate in CHF Pa&ents? Quadro Ormonale
Cor&solo (nmol/L)
Controlli = 308+94 CHF=631* +182 Insulina (uUL/ml)
Controlli = 13.2+7.6 CHF=10.7+4.0 Cor&solo/Insulina
Controlli = 23.3+12 CHF= 59.1*+25 *p<0.05
Increased Skeletal Muscle AA Release with Light Exercise in Decondi&oned Pa&ents with Heart Failure (Aquilani, Pasini et al: J Am Coll Cardiol 2005 )
• We evaluate the effects of light work (20 WaBs by cycleBe) on the net muscle release of AA
• We studied chronically stable untrained normonourished CHF pa=ents (NYHA II/III) + controls
• Net AAs uptake/release was calculated as A-‐V difference x leg flow (by catheters into and Femoral Artery and Vein)
• Blood AA concentra=on were measured by HPLC
NET AMINOACID UPTAKE AND RELEASE
Muscle amino acid net uptake and/or release at rest and during light exercise (20W) in controls (open bars) and chronic heart failure (CHF) patients (solid Bars)
Increased Skelatal Muscle AA Release with Light Exercise in DecondiFoned PaFents with Heart Failure
(J Am Coll Cardiol 2005 )
Cor&sol (nmol/L) Control = 297+78 CHF=703* +151
Insulin (uUL/ml) Control = 12.7+5.5 CHF=11.3+6.0
Cor&sol/Insulin Control = 23.4+9 CHF= 63.2*+28 *p<0.05
33
Cont. Cont. AAs
p-mTor m-Tor
Amino acids
mTor
Insulin
AA
p70S6K
S6
Protein Synthesis
4EBP1
IRS1-2
PI3K
AKT
GLUT4
GLUT4
Glucose
Glucose Uptake
Unknownmediator
Rheb TSC1/2
TNFα
p38MAPK
IKK
MMPsApoptosis
SOCS
StimulationInhibition
eNOS/NO
PGC1-α
Number/Functionof Mitochondria
ATP
ROS
Unknownmediator
Intracellular metabolism. The role of signalling via the mTor pathway and other routes
(Fla&, Pasini et al: Am J Cardiol 2008)
Health Issues can be pinpointed by assessing NEI imbalances ??? • Yes. But is a New Approach…
How??? • Measuring:
– Anabolic/Catabolic Circula=ng Molecules – Metabolic/Func=onal effects on body organs
• IntegraFng data