Cognitive effects may be linked to 19/11/2012

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1 Cognitive effects may be linked to 19/11/2012 active transport and urban air pollution Luc Int Panis 2012 Polis Conference Perugia Session: III A: The benefits of active travel

2 19/11/2012 2

3 New: neurological effects of air pollution 19/11/2012 3

4 New evidence for Neurological and cognitive effects» Recently, associations found between chronic exposure to air pollution and negative neurological effects.» Huge implications : respiratory<cardiovascular<neurological» Link between ishemic stroke and PM exposure is a well known ( cardiovascular ) effect. May impact brain function.» Post-mortem studies in Mexico city on children and dogs» Calderón-Garcidueñas L, Solt AC, Henríquez-Roldán C, et al. Long-term air pollution is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid β-42 and α-synuclein in children and young adults. Toxicol Pathol. 2008a; 36(2): » Calderón-Garcidueñas L, Mora-Tiscareño A, Ontiveros E, et al. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 2008b; 68(2): » Calderón-Garcidueñas L, Engle R, Mora-Tiscareño A, et al. Exposure to severe urban air pollution influences cognitive outcomes, brain volume and systemic inflammation in clinically healthy children. Brain Cogn. 2011; 77(3): /11/2012 4

5 New evidence for Neurological and cognitive effects» Calderon et al associations between urban pollution (O 3 and PM);» ultrafine particle deposition in the brain» Neuroinflammation, disruption of blood-brain barrier» accumulation of amyloid-β and α-synuclein» and cognitive decline» Others authors have found associations between PM exposure and cognitive decline.» Chen JC, Schwartz J. Neurobehavioral effects of ambient air pollution on cognitive performance in US adults. Neurotoxicology. 2009; 30(2): » Ranft U, Schikowski T, Sugiri D, Krutmann J, Krämer U. Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environ Res.2009;109(8): » Suglia SF, Gryparis A, Wright RO, Schwartz J, Wright RJ Association of black carbon with cognition among children in a prospective birth cohort study. Am J Epidemiol. 2008; 167(3):280-6.» J. Weuve, R. Puett, J. Schwartz, J.Yanosky, F. Laden, F. Grodstein. Exposure to particulate air pollution and cognitive decline in older women. Archives of internal medicine. 2012; 172(3): /11/2012 5

6 Physical activity» Good for respiratory and cardiovascular health Well known..but Goa et al AE in press Elevated cardiorespiratory fitness observed in physically activate children could be negated by increased amount of inhaled pollutants during exercise Cutrufello et al Sports Medicine healthy athletes. exercising in urban areas in close proximity to major roadways should consider ambient air pollution.prior to engaging in vigorous exercise» Good for memory, brain plasticity, cognition and mental health» Aerobic training improves cognitive and visuospatial memory» WHY?» mechanism for benefits of exercise remains to be elucidated.» Better blood transport to brain? (<> air pollution; Louwies et al EHP in prep)» exercise stimulates neurogenesis and synaptic plasticity» Even short bouts of exercise induce production and release of neurotrophines such as BDNF and SYN1 in blood and in the brain. (Brain Derived Neurotrophic Factor)» Our research hypothesis: Air pollution exposure cancels the neurological benefits of exercise 19/11/2012 6

7 Brain derived neurotrophic factor (BDNF) in urban cyclists (2011)» Physical exercise increases levels of Brain-Derived Neurotrophic Factor and this contributes to neural plasticity and improved learning and memory.» Increase in serum BNDF is absent after cycling in traffic.» Additional experiments in humans (cognition) and animals (brain) Bos I., Jacobs L., Nawrot T.S., de Geus, B., Torfs R., Int Panis L., Degraeuwe B., Meeusen, R. No exercise-induced increase in serum BDNF after cycling near a major traffic road. Neuroscience Letters 500 (2011) /11/2012 7

8 Start to Run experiment» Goal» Effects of aerobic training in urban and rural setting on: - cognition - inflammation - basal serum BDNF» Design» Inactive/sedentary voluntueers» 12 week Start-2-Run (S2R), 3 sessions/week» UFP- contrast» S2R in city (Brussels; n=21)» S2R in rural area (Mol; n=13)» Biological effects before & after S2R 19/11/2012 8

9 7/02/2011 9/02/ /02/ /02/ /02/ /02/ /02/ /02/ /02/ /02/ /02/2011 1/03/2011 3/03/2011 5/03/2011 7/03/2011 9/03/ /03/ /03/ /03/ /03/ /03/ /03/ /03/ /03/ /03/ /03/ /03/2011 2/04/2011 4/04/2011 6/04/2011 8/04/ /04/ /04/ /04/ /04/ /04/ /04/ /04/ /04/ /04/ /04/ /04/2011 2/05/2011 4/05/2011 Particle number (particles/cc) Small and variable UFP ( nm)contrast larger nano particle contrast (<20nm) Urban location Rural location /11/2012 9

10 Biological effects studied» Cognitive tests» Exhaled NO» Blood tests» Leucocytes» Serum BDNF» Gene expression 19/11/

11 Difference in white blood cells Results Normalized UFP accumulation Bos I., Vanparijs J., De Boever P., Pattyn N., Int Panis L., Meeusen R. Urban air pollution exposure during aerobic training: effects on inflammatory markers and cognition. Medicine & Science in Sports & Exercise, in press. 19/11/

12 UFP Dose - effect response for inflammation 19/11/

13 Effect of exercise and UFP in rodents» 4 groups of 6 Wistar rats exposed for 90 minutes to 1 of 4 conditions:» UFP (~ pt.cm -3 with a 8 nm peak) + exercise (20m.min -1 for 90 min)» UFP + rest» Ambient air + exercise» Ambient air + rest (control)» Gene expression analysis of» Olfactory bulb» Prefrontal cortex» Hippocampus 19/11/

14 Expression ratio Brain gene expression is changed with physical activity & UFP» BDNF and NFE2L2 hippocampal expression increases with ambient air/exercise» No BDNF up-regulation in the UFP-exposed group during exercise» Synapsin1 is down-regulated with UFP 2,5 2 * * UFP/Rest Ambient air/exercise UFP/Exercise 1,5 1 0,5 0 * BDNF IL1α IL1β NFE2L2 NOS2 NOS3 TNF - Bos I., De Boever P., Int Panis L., Sarre S., Meeusen R No up-regulation of hippocampal BDNF expression in rats exposed to UFP during exercise, Neuroscience - Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression 19/11/2012 and morphology 14 Fonken et al., 2011 in Molecular Psychiatry

15 Conclusions» Accumulating evidence for urban air pollution effect on the brain (e.g. review papers by Block et al in Neurotoxicology; Genc et al in J. of Toxicology)» Neuroinflammation, neurotoxicity,» Gene expression changes» Neurobehavioral changes, (spatial) learning,» Pathways of effect and neurotoxic fractions of PM not well known» Interaction with the active transport» Physical activity increased exposure» Physical activity comes with neurological benefits» Effects of both can be found even after short exposures with well designed studies (contrast, controls,.) Effects need to be taken into account when planning cities for active citizens 19/11/

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