ALTERAZIONI DELLA BIOENERGETICA

MITOCONDRIALE IN UN MODELLO ANIMALE DI

IPOPERFUSIONE CEREBRALE CRONICA

A. Romano1,3, G. Serviddio1, M. Lauriola1,2, F. Bellanti1, R. Tamborra1, M. Blonda1, G. Vendemiale1,2

1Cattedra di Geriatria, Università di Foggia2Medicina Interna, IRCCS Casa Sollievo della Sofferenza, San

Giovanni Rotondo, Foggia3Wolfson Centre for Age-Related Disease, King’s College, London

ISTOLOGIA

MASSA CEREBRALE

ALTERAZIONI REDOX

FLUSSO SANGUIGNO

Structural brain changes in aging: courses, causes and cognitiveconsequences. Fjell AM et al. Rev Neurosci. 2010;21(3):187‐221.

NEUROTRASMISSIONE

Mitochondrial impairment

CEREBRAL BLOOD FLOW•Risk factor for Alzheimer Disease •Alzheimer and Vascular Dementia share some clinical presentation symptoms

Mitochondria, oxidative metabolism and cell death in stroke. Sims N et al. BBA, 1802 (2010) 80–91

Cerebral perfusion and oxygenation differences in Alzheimer's disease risk. Neurobiol Aging. 2009 Nov;30(11):1737-48

Vascular risk factor detection and control may prevent Alzheimer’s disease. JC. de la Torre. Ageing Research Reviews 9 (2010) 218–225

Increase of ROS productionIncrease of ROS production

Decrease of Complex I and IV activityDecrease of Complex I and IV activity

Decrease of ATP synthesisDecrease of ATP synthesis

1 2 3

Modello animale ipoperf.

cerebrale

Mitocondrio ROS

AIMAIM

METHODS1. Chronic oligaemia was induced by permanent bilateral common carotid

artery occlusion* (2VO); the common carotid artery was doubly bilaterally legated just below the bifurcation with 5–0 silk suture and the artery was cut in between the ligations;

2. 3 months later, brain was removed, mitochondria respiratory chain function and rate of peroxide production was measured by , respectively, polarography and fluorimetry.

* Farksas et al. Brain Research Reviews 54, 2007, 162-180

Studio delle alterazioni comportamentali ed

istologiche in un modello animale di oligoemia

cerebrale cronica

M. Lauriola1,2, G. Serviddio1 , A. Romano1,, F. Bellanti1, T. Rollo1, G. Vendemiale1,2

1Cattedra di Geriatria, Università di Foggia2Medicina Interna, IRCCS Casa Sollievo della Sofferenza, San

Giovanni Rotondo, Foggia

MITOCHONDRIAL ACTIVITY-Respiratory Control Index-

COMPLEX I

COMPLEX II

MITOCHONDRIAL MEMBRANE POTENTIAL

MITOCHONDRIA PEROXIDE PRODUCTION

•Complex I: impaired phosphorylation efficiency

•Complex II: reduced oxygen consumption

•Collapse of mitochondrial membrane potential

•Increased H2O2 production from Complex I

•ATP CONTENT

•PROTON LEAK

UK UNIT

•REGENERATIVE PROCESSES

•HUMAN POST-MORTEM TISSUE ANALYSIS

TO DO

ALTERAZIONI DELLA BIOENERGETICA

MITOCONDRIALE IN UN MODELLO ANIMALE DI

IPOPERFUSIONE CEREBRALE CRONICA

A. Romano1,3, G. Serviddio1, M. Lauriola1,2, F. Bellanti1, R. Tamborra1, M. Blonda1, G. Vendemiale1,2

1Cattedra di Geriatria, Università di Foggia2Medicina Interna, IRCCS Casa Sollievo della Sofferenza, San

Giovanni Rotondo, Foggia3Wolfson Centre for Age-Related Disease, King’s College, London