1 tot 4 mensen in Nederland leidt aan een hersenziekte en daar komen er steeds meer bij. Het gaat hier met name om ziekten zoals Alzheimer, Parkinson en Beroertes. Van deze hersenziektes is de precieze oorzaak onduidelijk. Het is echter wel zo dat meerdere factoren uit de omgeving samen met een genetische aanleg een rol spelen.
Vooral de blootstelling aan het ultrafijne deel uit luchtverontreiniging lijkt zo’n factor te zijn. Er is in mensen een sterk verband aangetoond tussen fijnstof concentratie en een verhoogd risico op het krijgen van verschillende vormen van dementie, de zieke van Parkinson, beroerte en mogelijk diverse andere chronische aandoeningen van de hersenen.
Ultrafijnstof kan de hersenen binnen dringen op verschillende manieren, via de longen en via het reukorgaan. Vervolgens kunnen deze deeltjes door hun toxische eigenschappen processen beïnvloeden of versnellen die leiden tot de ontwikkeling van chronische hersenziekten.
De als het ware uit de luchtverontreiniging gezeefde ultrafijne deeltjes veroorzaken in het weefstel waar ze terecht komen oxidatieve stress. Oxidatieve stress is een stofwisselingstoestand, waarbij reactieve zuurstofverbindingen (reactieve oxygen species ROS) in de cel gevormd worden. Deze reactieve zuurstofverbindingen beschadigen celstructuren, zoals proteïnen, lipiden en DNA. Dit type beschadiging is geassocieerd met aandoeningen zoals Alzheimer en Parkinson. Daarbij wordt de complexe structuur op het oppervlak van het ultra-fijne deeltje door cellen van het immune systeem herkend als lichaamsvreemd; het ultra-fijne deeltje is extra immunogeen omdat het in verhouding een heel groot oppervlak heeft. Dit geldt ook voor de toxiciteit van het deeltje. In een poging om zich te ontdoen van de verontreiniging worden plaatselijke immuun cellen zoals macrofagen of gliacellen in het brein geactiveerd. Deze activatie geeft een constante bron van vrijkomende ontstekingsfactoren en meer ROS. Ook kunnen de deeltjes zelf betrokken zijn bij het ophopen van eiwit aggregaten zoals die gevonden worden in neurodegeneratieve aandoeningen.
Literatuur overzicht en disscussie ( review)
De relatie tussen neurodegeneratieve ziekten en deeltjes uit luchtvervuiling kwam voor het eerst aan het licht bij het bestuderen van hersenweefsel geïsoleerd uit zwerfhonden afkomstig uit stedelijk en luchtvervuild gebied van Mexico… etc hier de stukken dieper per aandoening en met referenties Hier meer inwijden over multifactoriële ziekten.
Ultrafijnstof effecten in de hersenen van volwassenen: Alzheimer Dementie en Parkinson
Notities: Ook hier is overlap tussen gewoon fijnstof met bepaalde stukken die we onder dit kopje hebben verzameld en ook hier is het waarschijnlijk dat juist het de UFP fractie de boosdoener is. De overlap moet, denk ik, worden verwerkt in een stukje algemeen. Misschien als een soort inleiding waarin we uitleggen wat het fijnstof is en dat ultrafijnstof een fractie is uit deze luchtverontreiniging (dus een vergelijking maken met een bak met knikkers)? Vervolgens zouden we kunnen uitleggen hoe het UFP lichaam binnen komt en waarom juist de ultra-fijnstof component relevant is hier.
Omdat UFP het beste in het lichaam kan doordringen (via de neus en longen en darmen) en het mechanismen in werking kan zetten die leiden tot een breed scala aan ziekten ( mechanismen systemische ontsteking, oxidatieve stress -> multifactoriële ziekten)
Epidemiologische studies naar Alzheimer, beroertes en Parkinson laten zien dat er een sterke associatie is met ‘’gemeten’’ PM2,5 of PM <2.5 en of uitlaatgassen. Ga je dieper kijken, bv in dier studies of humane secties dan vind je dus de ultra kleine deeltjes in het lichaam. Dit is waarom ik kriegel wordt van ‘’ultra-fijnstof daar weten we eigenlijk nog maar weinig van’’
Ik denk dat we moeten gaan van breed naar specifiek -> luchtvervuiling, uitlaatgassen, fijnstof naar ultra-fijnstof.
De scheiding tussen jongeren en volwassen is met betrekking tot toxische effecten aan het centrale zenuwstelsel niet zwart-wit. De opbouw tot het ontwikkelen van Alzheimer begint bijvoorbeeld al vroeg Dr. Lilian calderón-garcidueñas, een pionier, ziet luchtvervuiling als een dreiging voor de normale ontwikkeling van de hersenen bij kinderen. Ze meent at al vroeg in de jeugd de hersen schade oplopen dor luchtvervuiling waardoor mensen later in het leven sneller Alzheimer ontwikkelen. Haar werk werd in eerste instantie zeer bekritiseerd omdat het niet dubbel blind en gerandomiseerd onderzoek zou betreffen. Toch blijft ze publiceren, wordt ze veel geciteerd maar ze is veel verder gekomen, en werkt samen met verschillende groepen dus haar werk kan worden beschouwd als erg belangrijk in haar veld. Toch zijn haar papers bij het lezen wel een beetje ‘gek’ data vaak niet gekwantificeerd, figuren zijn niet echt kloppend. Controle groepen zijn lastig.
Ambient air pollution and neurotoxicity on brain structure: Evidence from women’s health initiative memory study
(Chen et al. 2015)
#PM and brain #older woman #neurotoxicity #epidemiology
OBJECTIVE: The aim of this study was to examine the putative adverse effects of ambient fine particulate matter (PM2.5 : PM with aerodynamic diameters <2.5mum) on brain volumes in older women. METHODS: We conducted a prospective study of 1,403 community-dwelling older women without dementia enrolled in the Women’s Health Initiative Memory Study, 1996-1998. Structural brain magnetic resonance imaging scans were performed at the age of 71-89 years in 2005-2006 to obtain volumetric measures of gray matter (GM) and normal-appearing white matter (WM). Given residential histories and air monitoring data, we used a spatiotemporal model to estimate cumulative PM2.5 exposure in 1999-2006. Multiple linear regression was employed to evaluate the associations between PM2.5 and brain volumes, adjusting for intracranial volumes and potential confounders. RESULTS: Older women with greater PM2.5 exposures had significantly smaller WM, but not GM, volumes, independent of geographical region, demographics, socioeconomic status, lifestyles, and clinical characteristics, including cardiovascular risk factors. For each interquartile increment (3.49mug/m(3) ) of cumulative PM2.5 exposure, the average WM volume (WMV; 95% confidence interval) was 6.23cm(3) (3.72-8.74) smaller in the total brain and 4.47cm(3) (2.27-6.67) lower in the association areas, equivalent to 1 to 2 years of brain aging. The adverse PM2.5 effects on smaller WMVs were present in frontal and temporal lobes and corpus callosum (all p values <0.01). Hippocampal volumes did not differ by PM2.5 exposure. INTERPRETATION: PM2.5 exposure may contribute to WM loss in older women. Future studies are needed to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other WM neuropathologies.
Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs
(Calderon-Garciduenas, Mora-Tiscareno, et al. 2008)
# Neuroinflammation #UFP in brain # children #dogs # pioneer study #cognition # neurotoxicity
Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.
Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults
(Calderon-Garciduenas, Solt, et al. 2008) in dropbox march
#Human #observational # Neuroinflammation # Alzheimer # UFP #Children
Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer’s and Parkinson’s diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer’s disease if they reside in a polluted environment.
Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer’s Disease Development
(Gonzalez-Maciel et al. 2017) In dropbox
#development Alzheimer # UFP in brain tissue #neuro toxicity in dogs and humans ( e.g. Control ed a bit strange)
Note: UFP and not PM ( small fractions in the brain tissue!
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer’s disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Abeta1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson’s disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites’ brains. Using transmission electron microscopy, we documented CDNPs in neurons, glia, choroid plexus, and neurovascular units of young MC residents versus matched clean air controls. CDNPs are associated with pathology in mitochondria, endoplasmic reticulum (ER), mitochondria-ER contacts (MERCs), axons,and dendrites. There is a significant difference in size and numbers between spherical CDNPs (>85%) and the angular, euhedral endogenous NPs (<15%). Spherical CDNPs (dogs 21.2+/-7.1 nm in diameter versus humans 29.1+/-11.2 nm, p = 0.002) are present in neurons, glia, choroid plexus, endothelium, nasal and olfactory epithelium, and in CSF at significantly higher in numbers in MC residents (p < 0.0001). Degenerated MERCs, abnormal mitochondria, and dilated ER are widespread, and CDNPs in close contact with neurofilaments, glial fibers, and chromatin are a potential source for altered microtubule dynamics, mitochondrial dysfunction, accumulation and aggregation of unfolded proteins, abnormal endosomal systems, altered insulin signaling, calcium homeostasis, apoptotic signaling, autophagy, and epigenetic changes. Highly oxidative, ubiquitous CDNPs constitute a novel path into AD pathogenesis. Exposed children and young adults need early neuroprotection and multidisciplinary prevention efforts to modify the course of AD at early stages
Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis
(Braithwaite et al. 2019) in dropbox
PM 1, Pm 2,5 en PM 10 en associatie met mental health outcomes zoals depressie, angst, bipolair, psychose en suicide.
BACKGROUND: Particulate air pollution’s physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, there is increasing interest in emerging evidence supporting a possible etiological link. OBJECTIVES: This systematic review aims to provide a comprehensive overview and synthesis of the epidemiological literature to date by investigating quantitative associations between PM and multiple adverse mental health outcomes (depression, anxiety, bipolar disorder, psychosis, or suicide). METHODS: We undertook a systematic review and meta-analysis. We searched Medline, PsycINFO, and EMBASE from January 1974 to September 2017 for English-language human observational studies reporting quantitative associations between exposure to PM 6 months) PM2:5 exposure and depression (n= 5 studies), the pooled odds ratio was 1.102 per 10-lg=m3 PM2:5 increase (95% CI: 1.023, 1.189; I2 = 0:00%). Two of the included studies investigating associations between long-term PM2:5 exposure and anxiety also reported statistically significant positive associations, and we found a statistically significant association between short-term PM10 exposure and suicide in meta-analysis at a 0-2 d cumulative exposure lag. DISCUSSION: Our findings support the hypothesis of an association between long-term PM2:5 exposure and depression, as well as supporting hypotheses of possible associations between long-term PM2:5 exposure and anxiety and between short-term PM10 exposure and suicide. The limited literature and methodological challenges in this field, including heterogeneous outcome definitions, exposure assessment, and residual confounding, suggest further high-quality studies are warranted to investigate potentially causal associations between air pollution and poor mental health. https://doi.org/ 10.1289/EHP4595
Cell-based assays that predict in vivo neurotoxicity of urban ambient nano-sized particulate matter(Zhang et al. 2019) in dropbox
#Alzheimer #animal model #mechanism #toxicity UPF fractions #neurotoxicity # In vitro
Exposure to urban ambient particulate matter (PM) is associated with risk of Alzheimer’s disease and accelerated cognitive decline in normal aging. Assessment of the neurotoxic effects caused by urban PM is complicated by variations of composition from source, location, and season. We compared several in vitro cell-based assays in relation to their in vivo neurotoxicity for NF-κB transcriptional activation, nitric oxide induction, and lipid peroxidation. These studies compared batches of nPM, a nanosized subfraction of PM2.5, extracted as an aqueous suspension, used in prior studies. In vitro activities were compared with in vivo responses of mice chronically exposed to the same batch of nPM. The potency of nPM varied widely between batches for NF-κB activation, analyzed with an NF-κB reporter in human monocytes. Three independently collected batches of nPM had corresponding differences to responses of mouse cerebral cortex to chronic nPM inhalation, for levels of induction of pro-inflammatory cytokines, microglial activation (Iba1), and soluble Aβ40 & -42 peptides. The in vitro responses of BV2 microglia for NO-production and lipid peroxidation also differed by nPM batch, but did not correlate with in vivo responses. These data confirm that batches of nPM can differ widely in toxicity. The in vitro NF-κB reporter assay offers a simple, high throughput screening method to predict the in vivo neurotoxic effects of nPM exposure.
Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro and in vivo
(Woodward et al. 2017).
#inflammation #mechanism #cognitive decline #brain # fractions UFP<200nm
Note: check exposure! 300ug/ml would be 3g/m3 high e.g upper limit is 20ug/m3 1500000X…. in other study from the same group 300ug/m3 might be an
Exposure to traffic-related air pollution (TRAP) is associated with accelerated cognitive aging and higher dementia risk in human populations. Rodent brains respond to TRAP with activation of astrocytes and microglia, increased inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4 (TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung macrophage responses to air pollution.
To further analyze these mechanisms, we examined mixed glial cultures (astrocytes and microglia) for RNA responses to nanoscale particulate matter (nPM; diameter <0.2 μm), a well-characterized nanoscale particulate matter subfraction of TRAP collected from a local freeway (Morgan et al. Environ Health Perspect 2011; 119,1003-1009, 2011). The nPM was compared with responses to the endotoxin lipopolysaccharide (LPS), a classic TLR4 ligand, using Affymetrix whole genome microarray in rats. Expression patterns were analyzed by significance analysis of microarrays (SAM) for fold change and by weighted gene co-expression network analysis (WGCNA) to identify modules of shared responses between nPM and LPS. Finally, we examined TLR4 activation in hippocampal tissue from mice chronically exposed to nPM.
SAM and WGCNA analyses showed strong activation of TLR4 and NF-κB by both nPM and LPS. TLR4 siRNA attenuated TNFα and other inflammatory responses to nPM in vitro, via the MyD88-dependent pathway. In vivo, mice chronically exposed to nPM showed increased TLR4, MyD88, TNFα, and TNFR2 RNA, and decreased NF-κB and TRAF6 RNA TLR4 and NF-κB responses in the hippocampus. These results show TLR4 activation is integral in brain inflammatory responses to air pollution, and warrant further study of TLR4 in accelerated cognitive aging by air pollution
Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts(Cacciottolo et al. 2020)
#Alzheimer #model # UFP #Mechanism
Exposure 300ug/m3 (10X okay)
Erratum in Corrigendum to “Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts” [FRBM 147C (2019) 242-251]. [Free Radic Biol Med. 2020]
Traffic-related air pollution particulate matter (TRAP-PM) is associated with increased risk of Alzheimer Disease (AD). Rodent models respond to nano-sized TRAP-PM (nPM) with increased production of amyloid Aβ peptides, concurrently with oxidative damage. Because pro-Aβ processing of the amyloid precursor protein (APP) occurs on subcellular lipid rafts, we hypothesized that oxidative stress from nPM exposure would alter lipid rafts to favor Aβ production. This hypothesis was tested with J20 mice and N2a cells transgenic for hAPPswe (familial AD). Exposure of J20-APPswe mice to nPM for 150 h caused increased lipid oxidation (4-HNE) and increased the pro-amyloidogenic processing of APP in lipid raft fractions in cerebral cortex; the absence of these changes in cerebellum parallels the AD brain region selectivity for Aβ deposits. In vitro, nPM induced similar oxidative responses in N2a-APPswe cells, with dose-dependent production of NO, oxidative damage (4-HNE, 3NT), and lipid raft alterations of APP with increased Aβ peptides. The antioxidant N-acetyl-cysteine (NAC) attenuated nPM-induced oxidative damage and lipid raft alterations of APP processing. These findings identify neuronal lipid rafts as novel targets of oxidative damage in the pro-amyloidogenic effects of air pollution. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models
(Cacciottolo et al. 2017) in dropbox ( used in Lelystad Airport gezondheid)
#Dementia #Nano-scale subfraction of urban PM2.5 designated as nPM (<200nm) #epidemiology and animal study combined #Genes and environment
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer’s disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women’s Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE varepsilon4/4 carriers. Female EFAD transgenic mice (5xFAD(+/-)/human APOE varepsilon3 or varepsilon4(+/+)) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral beta-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Abeta deposits, both exacerbated by APOE varepsilon4. Moreover, nPM exposure increased Abeta oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in varepsilon4 carriers. The underlying mechanisms may involve increased cerebral Abeta production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.
Glutamatergic Neurons in Rodent Models Respond to Nanoscale Particulate Urban Air Pollutants in Vivo and in Vitro
(Morgan et al. 2011) In dropbox and in lelystad airport #
BACKGROUND: Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented. OBJECTIVE: We evaluated rodent brain responses to urban nanoscale (< 200 nm) PM (nPM). METHODS: Ambient nPM collected near an urban freeway was transferred to aqueous suspension and reaerosolized for 10-week inhalation exposure of mice or directly applied to rat brain cell cultures. RESULTS: Free radicals were detected by electron paramagnetic resonance in the nPM 30 days after initial collection. Chronic inhalation of reaerosolized nPM altered selected neuronal and glial activities in mice. The neuronal glutamate receptor subunit (GluA1) was decreased in hippocampus, whereas glia were activated and inflammatory cytokines were induced [interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNFalpha)] in cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24-48 hr of exposure that involved glutamatergic functions. In hippocampal slice cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)-amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite outgrowth, also blocked by AP5. Induction of IL-1alpha and TNFalpha in mixed glia cultures required higher nPM concentrations than did neuronal effects. Because conditioned media from nPM-exposed glia also impaired outgrowth of embryonic neurites, nPM can act indirectly, as well as directly, on neurons in vitro. CONCLUSIONS: nPM can affect embryonic and adult neurons through glutamatergic mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest that cerebral ischemia, which involves glutamatergic excitotoxicity, could be exacerbated by nPM.
Urban traffic-derived nano particulate matter reduces neurite outgrowth via TNFα in vitro.
(Cheng et al. 2016) In drobox (journal of neuro-inflammation, impact factor 5)
#in vitro- data, #mechanism, #inflammation, #neurodegeneration
The basis for air pollution-associated neurodegenerative changes in humans is being studied in rodent models. We and others find that the ultrafine particulate matter (PM) derived from vehicular exhaust can induce synaptic dysfunction and inflammatory responses in vivo and in vitro. In particular, a nano-sized subfraction of particulate matter (nPM, PM0.2) from a local urban traffic corridor can induce glial TNFα production in mixed glia (astrocytes and microglia) derived from neonatal rat cerebral cortex.Here, we examine the role of TNFα in neurite dysfunctions induced by nPM in aqueous suspensions at 12 μg/ml. First, we show that the proximal brain gateway to nPM, the olfactory neuroepithelium (OE), rapidly responds to nPM ex vivo, with induction of TNFα, activation of macrophages, and dendritic shrinkage. Cell interactions were further analyzed with mixed glia and neurons from neonatal rat cerebral cortex. Microglia contributed more than astrocytes to TNFα induction by nPM. We then showed that the threefold higher TNFα in conditioned media (nPM-CM) from mixed glia was responsible for the inhibition of neurite outgrowth by small interfering RNA (siRNA) TNFα knockdown and by TNFα immunoneutralization. Despite lack of TNFR1 induction by nPM in the OE, experimental blocking of TNFR1 by TNFα receptor blockers restored total neurite length. These findings implicate microglia-derived TNFα as a mediator of nPM in air pollution-associated neurodegenerative changes which alter synaptic functions and neuronal growth..
Selective memory and behavioral alterations after ambient ultrafine particulate matter exposure in aged 3xTgAD Alzheimer’s disease mice
(Jew et al. 2019)
#animal #Alzheimer’s disease #relevant exposure # clear paper!
Background: A growing body of epidemiological literature indicates that particulate matter (PM) air pollution exposure is associated with elevated Alzheimer’s disease (AD) risk and may exacerbate AD-related cognitive decline. Of concern is exposure to the ultrafine PM (UFP) fraction (≤100 nm), which deposits efficiently throughout the respiratory tract, has higher rates of translocation to secondary organs, like brain, and may induce inflammatory changes. We, therefore, hypothesize that exposure to UFPs will exacerbate cognitive deficits in a mouse model of AD. The present study assessed alterations in learning and memory behaviors in aged (12.5 months) male 3xTgAD and non-transgenic mice following a 2-week exposure (4-h/day, 4 days/week) to concentrated ambient UFPs using the Harvard ultrafine concentrated ambient particle system (HUCAPS) or filtered air. Beginning one month following exposure, locomotor activity, spatial learning and memory, short-term recognition memory, appetitive motivation, and olfactory discrimination were assessed.
Results: No effects on locomotor activity were found following HUCAPS exposure (number concentration, 1 × 104-4.7 × 105 particles/cm3; mass concentration, 29-132 μg/m3). HUCAPS-exposed mice, independent of AD background, showed a significantly decreased spatial learning, mediated through reference memory deficits, as well as short-term memory deficits in novel object recognition testing. AD mice displayed diminished spatial working memory, potentially a result of olfactory deficits, and short-term memory. AD background modulated HUCAPS-induced changes on appetitive motivation and olfactory discrimination, specifically enhancing olfactory discrimination in NTg mice. Modeling variation in appetitive motivation as a covariate in spatial learning and memory, however, did not support the conclusion that differences in motivation significantly underlie changes in spatial learning and memory.
Conclusions: A short-term inhalation exposure of aged mice to ambient UFPs at human-relevant concentrations resulted in protracted (testing spanning 1-6.5 months post-exposure) adverse effects on multiple memory domains (reference and short-term memory) independent of AD background. Impairments in learning and memory were present when accounting for potential covariates like motivational changes and locomotor activity. These results highlight the need for further research into the potential mechanisms underlying the cognitive effects of UFP exposure in adulthood.
A Voxel-Based Morphometry Study Reveals Local Brain Structural Alterations Associated with Ambient Fine Particles in Older Women
(Casanova et al. 2016) in dropbox
#Humans #Neurotoxicity #Dementia #PM #association with PM.2.5 concentrations brain is UFP
Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters < 2.5 mum) has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure. Methods: Brain MRI data were obtained from 1365 women (aged 71-89) in the Women’s Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space). Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average) exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM) and white matter (WM) maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked smaller WM volumes to PM2.5, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.