International journal of science – 05.Sep.2013
Topoisomerases are expressed throughout the developing and adult brain and are mutated in some individuals with autism spectrum disorder (ASD). However, how topoisomerases are mechanistically connected to ASD is unknown. Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor, dose-dependently reduces the expression of extremely long genes in mouse and human neurons, including nearly all genes that are longer than 200 kilobases. Expression of long genes is also reduced after knockdown of Top1 or Top2b in neurons, highlighting that both enzymes are required for full expression of long genes. By mapping RNA polymerase II density genome-wide in neurons, we found that this length-dependent effect on gene expression was due to impaired transcription elongation. Interestingly, many high-confidence ASD candidate genes are exceptionally long and were reduced in expression after TOP1 inhibition. Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders.
Immunologic research – Jul.2013
Authors and affiliations
C. A. Shaw – 1,2,3
L. Tomljenovic – 1
1.Neural Dynamics Research Group, Department of Ophthalmology and Visual SciencesUniversity of British Columbia (UBC)VancouverCanada
2.Program in Experimental MedicineUniversity of British Columbia (UBC)VancouverCanada
3.Program in NeuroscienceUniversity of British Columbia (UBC)VancouverCanada
We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer’s and has been linked to this disease and to the Guamanian variant, ALS–PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.
US National Library of Medicine
National Institutes of Health – Jun 2014
Li X, Qu F, Xie W, Wang F, Liu H, Song S, Chen T, Zhang Y, Zhu S, Wang Y, Guo C, Tang TS.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Thimerosal is a vaccine antimicrobial preservative which has long been suspected an iatrogenic factor possibly contributing to neurodevelopmental disorders including autism. The association between infant vaccine thimerosal exposure and autism remains an open question. Although thimerosal has been removed from mandatory childhood vaccines in the United States, thimerosal-preserved vaccines are still widely used outside of the United States especially in developing countries. Notably, thimerosal-containing vaccines are being given to the newborns within the first 12-24 h after birth in some countries. To examine the possible neurotoxic effects of early neonatal exposure to a higher level of thimerosal, FVB mice were subcutaneously injected with thimerosal-mercury at a dose which is 20× higher than that used for regular Chinese infant immunization during the first 4 months of life. Thimerosal-treated mice exhibited neural development delay, social interaction deficiency, and inclination of depression. Apparent neuropathological changes were also observed in adult mice neonatally treated with thimerosal. High-throughput RNA sequencing of autistic-behaved mice brains revealed the alternation of a number of canonical pathways involving neuronal development, neuronal synaptic function, and the dysregulation of endocrine system. Intriguingly, the elevation of anterior pituitary secreting hormones occurred exclusively in male but not in female thimerosal-treated mice, demonstrating for the first time the gender bias of thimerosal-mercury toxicity with regard to endocrine system. Our results indicate that higher dose of neonatal thimerosal-mercury (20× higher than that used in human) is capable of inducing long-lasting substantial dysregulation of neurodevelopment, synaptic function, and endocrine system, which could be the causal involvements of autistic-like behavior in mice.
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1 Corinthians 15 Authorized (King James) Version (AKJV)
1 Moreover, brethren, I declare unto you the gospel which I preached unto you, which also ye have received, and wherein ye stand;
2 by which also ye are saved, if ye keep in memory what I preached unto you, unless ye have believed in vain.
3 For I delivered unto you first of all that which I also received, how that Christ died for our sins according to the scriptures;
4 and that he was buried, and that he rose again the third day according to the scriptures:
Hebrews 6 Authorized (King James) Version (AKJV)
1 Therefore leaving the principles of the doctrine of Christ, let us go on unto perfection; not laying again the foundation of repentance from dead works, and of faith toward God,
2 of the doctrine of baptisms, and of laying on of hands, and of resurrection of the dead, and of eternal judgment.
3 And this will we do, if God permit.
4 For it is impossible for those who were once enlightened, and have tasted of the heavenly gift, and were made partakers of the Holy Ghost,
5 and have tasted the good word of God, and the powers of the world to come,
6 if they shall fall away, to renew them again unto repentance; seeing they crucify to themselves the Son of God afresh, and put him to an open shame.
7 For the earth which drinketh in the rain that cometh oft upon it, and bringeth forth herbs meet for them by whom it is dressed, receiveth blessing from God:
8 but that which beareth thorns and briers is rejected, and is nigh unto cursing; whose end is to be burned.
1 Who hath believed our report? and to whom is the arm of the Lord revealed?
2 For he shall grow up before him as a tender plant,and as a root out of a dry ground:he hath no form nor comeliness;and when we shall see him,there is no beauty that we should desire him.
3 He is despised and rejected of men;a man of sorrows, and acquainted with grief:and we hid as it were our faces from him;he was despised, and we esteemed him not.
4 Surely he hath borne our griefs,and carried our sorrows:yet we did esteem him stricken,smitten of God, and afflicted.
5 But he was wounded for our transgressions,he was bruised for our iniquities:the chastisement of our peace was upon him;and with his stripes we are healed.
6 All we like sheep have gone astray;we have turned every one to his own way;and the Lord hath laid on him the iniquity of us all.
7 He was oppressed, and he was afflicted,yet he opened not his mouth:he is brought as a lamb to the slaughter,and as a sheep before her shearers is dumb,so he openeth not his mouth.
8 He was taken from prison and from judgment:and who shall declare his generation? for he was cut off out of the land of the living:for the transgression of my people was he stricken.
9 And he made his grave with the wicked,and with the rich in his death;because he had done no violence,neither was any deceit in his mouth.
10 Yet it pleased the Lord to bruise him;he hath put him to grief:when thou shalt make his soul an offering for sin,he shall see his seed, he shall prolong his days,and the pleasure of the Lord shall prosper in his hand.
11 He shall see of the travail of his soul, and shall be satisfied:by his knowledge shall my righteous servant justify many;for he shall bear their iniquities.
12 Therefore will I divide him a portion with the great,and he shall divide the spoil with the strong;because he hath poured out his soul unto death:and he was numbered with the transgressors;and he bare the sin of many,and made intercession for the transgressors.