Environmental exposure, obesity, and Parkinson's disease: lessons from fat and old worms.
BACKGROUND
A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson's disease (PD). This link may help to elucidate mechanisms of neurotoxicity.


OBJECTIVE
We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson's disease (PD), with an emphasis on the neurotransmitter, dopamine (DA).


METHODS
A PubMed literature search was performed using the terms "obesity" and any of the following: "C. elegans," "central nervous system," "neurodegeneration," "heavy metals," "dopamine" or "Parkinson's disease." We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases.


METHODS
Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal- and chemical-induced neurodegeneration.


CONCLUSIONS
One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.
Aitlhadj
Layla
L
King's College London, Pharmaceutical Science Division, London, United Kingdom.
Avila
Daiana Silva
DS
Benedetto
Alexandre
A
Aschner
Michael
M
Stürzenbaum
Stephen Richard
SR
D000367:Age Factors; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects / Q000706:statistics & numerical data*; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000633:toxicity; D062665:Epidemiological Monitoring; D006801:Humans; D008670:Metals / Q000633:toxicity; D023421:Models, Animal; D009765:Obesity / Q000453:epidemiology* / Q000209:etiology; D010300:Parkinson Disease / Q000453:epidemiology* / Q000209:etiology
D004785:Environmental Pollutants; D008670:Metals
Dev Biol. 1977 Mar;56(1):110-56
838129
Obesity (Silver Spring). 2008 Jan;16(1):119-24
18223623
Mech Ageing Dev. 2010 May;131(5):364-5
20236608
J Nutr. 2008 May;138(5):841-8
18424589
J Neurosci Methods. 2010 Apr 30;188(1):58-61
20149821
Biochem Pharmacol. 2007 Jul 15;74(2):177-90
17416354
Mol Pharmacol. 1998 Oct;54(4):601-9
9765501
Genes Dev. 2003 Aug 1;17(15):1882-93
12869585
Neuroscience. 2002;115(4):1335-46
12453501
Science. 2003 Oct 31;302(5646):841
14593171
Nucleic Acids Res. 1986 Jun 11;14(11):4577-89
3520487
J Neurochem. 2007 Apr;101(2):313-26
17217412
J Biol Chem. 2009 Dec 18;284(51):35758-68
19801673
BMC Biol. 2009 Jun 22;7:33
19545405
Ann N Y Acad Sci. 2004 Mar;1012:115-28
15105259
Hum Mol Genet. 2004 Feb 1;13(3):303-14
14662656
Neurobiol Dis. 2010 Feb;37(2):330-8
19850127
J Neurochem. 2006 Jun;97(6):1611-26
16805772
Cell Metab. 2009 Nov;10(5):430-5
19883620
Diabetologia. 1980 Aug;19(2):148-53
7418967
Int J Biol Sci. 2010 Jan 07;6(1):9-50
20087441
Environ Health Perspect. 2010 Aug;118(8):1071-80
20403794
Nat Rev Genet. 2002 Aug;3(8):622-30
12154385
PLoS Genet. 2010 Aug 26;6(8):
20865164
Prog Brain Res. 2008;168:145-53
18166392
Neurosci Lett. 1988 Sep 12;91(3):349-53
3141846
Proc R Soc Lond B Biol Sci. 1953 Jan 15;140(901):578-96
13027283
Neuron. 2000 Jun;26(3):619-31
10896158
Chem Rev. 2009 Oct;109(10):4862-84
19534496
Nature. 2003 Jan 16;421(6920):268-72
12529643
Science. 1995 Jul 28;269(5223):543-6
7624777
J Mol Neurosci. 2007;31(2):127-37
17478886
Mech Ageing Dev. 2003 Jul;124(7):779-800
12875742
Biochim Biophys Acta. 2009 Jun;1791(6):474-8
19168149
Development. 2003 Apr;130(8):1621-34
12620986
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):728-33
18182484
Int J Epidemiol. 2008 Oct;37(5):1008-17
18579573
Dev Biol. 1980 Aug;78(2):542-76
7409314
Proc Natl Acad Sci U S A. 1985 Apr;82(7):2173-7
3872460
Mol Med. 1997 Jan;3(1):37-48
9132278
J Neurosci. 1993 Dec;13(12):5407-17
8254383
J Biol Chem. 2001 Sep 7;276(36):34013-8
11418603
Neurodegener Dis. 2004;1(4-5):175-83
16908987
Cien Saude Colet. 2008 Jan-Feb;13(1):269-81
18813540
Nature. 1995 May 4;375(6526):73-8
7723846
Toxicol Appl Pharmacol. 2009 Oct 15;240(2):273-85
19646462
FEBS J. 2010 Jun;277(11):2531-42
20553489
Physiol Behav. 2008 Sep 3;95(1-2):168-75
18619628
Genes Nutr. 2010 Mar;5(1):17-27
19936816
Pharmacol Res. 2006 Nov;54(5):361-72
16962336
Exp Gerontol. 2005 Nov;40(11):850-6
16221538
Science. 2001 Jun 15;292(5524):2041-50
11375483
Diabetes. 2006 Oct;55(10):2876-82
17003356
Brain Res. 1999 Dec 18;851(1-2):254-7
10642852
Annu Rev Entomol. 2005;50:447-77
15355245
Cell Metab. 2008 Mar;7(3):249-57
18316030
Science. 1989 Jan 20;243(4889):398-400
2563176
Genes Dev. 2005 Oct 1;19(19):2278-83
16166371
Development. 1999 Dec;126(24):5819-31
10572056
Eur J Pharmacol. 1976 Apr;36(2):363-71
6286
Med Hypotheses. 2010 Mar;74(3):578-89
19800745
J Clin Invest. 1997 Oct 1;100(7):1750-4
9312173
Ann Neurol. 2006 Aug;60(2):248-52
16862581
PLoS One. 2007 Jun 06;2(6):e504
17551584
WormBook. 2007 Mar 09;:1-20
18050496
Curr Alzheimer Res. 2006 Sep;3(4):311-26
17017862
Biochem Soc Trans. 2006 Feb;34(Pt 1):77-80
16417487
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14658-63
17804796
Biochemistry. 1980 Jun 24;19(13):2873-82
7397109
Environ Health Perspect. 2005 Sep;113(9):1263-70
16140639
Science. 1998 Dec 11;282(5396):2028-33
9851919
Pol J Pharmacol. 2002 Nov-Dec;54(6):573-9
12866711
J Neurosci. 1995 Oct;15(10):6975-85
7472454
Mol Neurobiol. 2001 Aug-Dec;24(1-3):99-106
11831557
J Neurosci. 2004 Feb 4;24(5):1217-25
14762140
J Neurochem. 2003 Jul;86(1):165-72
12807436
J Alzheimers Dis. 2008 Sep;15(1):29-44
18780965
Lab Invest. 2005 Apr;85(4):452-63
15723088
Physiol Behav. 1998 Mar;63(5):829-35
9618006
BMJ. 2010 Feb 09;340:c824
20144986
J Neurosci. 2009 Jun 3;29(22):7302-14
19494152
Methods Enzymol. 1998;296:529-47
9779472
Neurotox Res. 2003;5(5):307-13
14715449
Philos Trans R Soc Lond B Biol Sci. 1986 Nov 12;314(1165):1-340
22462104
J Alzheimers Dis. 2005 Nov;8(2):183-200; discussion 209-15
16308487
Neurotoxicology. 2009 Nov;30(6):926-33
19781568
Dev Cell. 2003 Jan;4(1):131-42
12530969
J Neural Transm (Vienna). 1996;103(8-9):987-1041
9013391
Neurochem Res. 2004 Jul;29(7):1365-9
15202766
Parkinsonism Relat Disord. 2001 Jul;7(3):177-183
11331184
Cell Metab. 2008 Jun;7(6):533-44
18522834
Curr Neuropharmacol. 2009 Mar;7(1):65-74
19721819
Ann Neurol. 2004 Jul;56(1):149-62
15236415
Teratology. 1994 Aug;50(2):125-36
7801300
Cell Metab. 2005 Jul;2(1):35-42
16054097
J Comp Neurol. 1975 Sep 15;163(2):215-26
240872
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3264-9
11867711
Toxicol Appl Pharmacol. 2007 Jun 1;221(2):131-47
17466353
J Biol Chem. 2005 Dec 30;280(52):42655-42668
16239214
Trends Neurosci. 2007 Aug;30(8):375-81
17604133
IUBMB Life. 2001 Apr;51(4):263-8
11569921
Science. 1998 Dec 11;282(5396):2012-8
9851916
Neurotoxicology. 2008 Jul;29(4):569-76
18565586
J Neural Transm Suppl. 1997;50:55-66
9120425
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):4016-21
18299572
WormBook. 2007 Mar 08;:1-22
18050505
J Neurosci. 1999 Jan 1;19(1):72-84
9870940
WormBook. 2007 Feb 20;:1-15
18050501
Curr Biol. 2007 Apr 3;17(7):592-8
17346966
Metabolism. 2009 Nov;58(11):1643-8
19616267
Genetics. 2009 Jan;181(1):153-63
19001289
Environ Health Perspect. 2009 Mar;117(3):325-32
19337503
J Exp Biol. 2003 Jan;206(Pt 2):223-31
12477893
Cell Res. 2008 Sep;18(9):978-81
19160545
Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):593-618
16724276
J Am Coll Cardiol. 2010 Jan 26;55(4):357-67
20117442
Pharmacol Biochem Behav. 2004 Feb;77(2):245-51
14751451
Proc Biol Sci. 2009 Mar 7;276(1658):789-97
19129111
Nature. 1996 Apr 11;380(6574):534-8
8606774
BMC Dev Biol. 2006 Oct 04;6:45
17020605
Ann Neurol. 2006 Aug;60(2):253-5
16862591
J Biol Chem. 2009 Jun 12;284(24):16482-16491
19251702
Science. 1982 May 28;216(4549):1012-4
6805073
Eur J Neurosci. 1996 Jun;8(6):1256-64
8752596
Environ Health Perspect. 2007 Jul;115(7):1002-6
17637913
Neurosci Bull. 2008 Apr;24(2):73-8
18369385
BMC Neurol. 2005 Dec 02;5:23
16321166
Neurotoxicol Teratol. 2002 Sep-Oct;24(5):639-53
12200195
Dev Biol. 1976 Jul 1;51(1):23-33
988845
Curr Top Cell Regul. 1984;24:153-69
6149889
Cell. 2008 Mar 21;132(6):1025-38
18358814
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13496-501
16157872
PLoS One. 2009 Nov 18;4(11):e7792
19924247
Neuroscience. 2008 Jul 17;154(4):1297-307
18550292
Pharmacol Ther. 2007 Feb;113(2):369-77
17084903
Nat Genet. 2009 Mar;41(3):308-15
19182805
Nat Genet. 2006 Mar;38(3):363-8
16462744
Physiol Behav. 2007 Aug 15;91(5):473-8
17137609
Aging Cell. 2008 Jan;7(1):13-22
17996009
Neuroimage. 2006 Jul 15;31(4):1419-25
16545583
J Proteome Res. 2009 Jul;8(7):3512-9
19466807
Science. 1995 Jul 28;269(5223):546-9
7624778
J Neurosci. 1999 Feb 15;19(4):1284-93
9952406