Porto a vostra conoscenza un altra via di ricerca sull' autismo e, essendo non esperto di genetica, lo sottopongo alla vostra attenzione. L' ormone ossitocina, volgarmente detto ``l' ormone dell' amore", e' un ormone dei mammiferi che agisce anche come neurotrasmettitore nel cervello. Recentemente si e' iniziato lo studio del ruolo dell' ossitocina in vari comportamenti, inclusi l' orgasmo,il riconoscimento sociale,l' affinita' delle coppie. l' ansia, l' amore ed il comportamento materno.In questo spettro di applicazioni nell' uomo non poteva mancare l' autismo. Personalmente io sono molto piu' convinto del ruolo degli ormoni sociali (come l' ossitocina) che non del ruolo di fantasmi noti come ``mirrors" venuti alla ribalta della stampa per opera di un gruppo di ricercatori dell' universita' di Parma che applicavano la mancanza di tali mirrors all' autismo. Infatti un gruppo di ricercatori americani dell' universita' di Miami e dell' universita' di Duke hanno concentrato le loro attenzioni sull' ossitocina come causa dell' autismo. Questa notizia mi e' pervenuta tramite la lista dell' autismo ``apana" degli stati uniti che l'avevano ricevuta dal PhD Gail Schrimmer. Allego il mail ricevuto in calce. Essi trovano che: ``In campioni di sangue e di tessuti del cervello lo stato di metilazione dei nucleotidi specifici nel gene del recettore della ossitocina e' significamente piu' alto in autistici (circa 70 percento) confrontato con la popolazione di controllo ove e' circa il 40 percento". Precedenti ricerche avevano trovato che dando l' ossitocina ad autistici la loro capacita' di socializzare aumentava. Inoltre, come si puo' vedere dal mail qui accluso contenente pagine di ricerche su ossitocina ed autismo, sarebbe la prima volta che viene coinvolto un meccanismo diverso dalla suscettivita genetica o istabilita' del genoma cioe' meccanismi tipicamente genetici; infatti la metilazione dei recettori puo' avere come effetto una minore sensibilita' all' ormone. Invito coloro che sono esperti di genetica di esprimere il loro parere su questa nuova via verso la comprensione dell' autismo. Fortini Pierluigi PS: sopra ho detto che sono ``piu' convinto dell' effetto del ruolo degli ormoni sociali sull' autismo" che altri meccanismi cervellotici tipo ``mirrors". La mia idea personale pero' non coincide con quanto e' detto dagli americani sulla ossitocina: in vari mail ho espresso la mia convinzione che l' autismo e' il risultato di un meccanismo genetico che colpisce le sinapsi del sistema nervoso parasimpatico perche' tutte le malformazioni presenti nell' autismo si manifestono come coinvolgenti le funzioni del sistema parasimpatico in primis il nervo vago. Su questa linea si stanno muovendo il Prof. Bourgeron di Parigi ed i Prof. Benfenati di Genova. Quest' ultimo ha ricevuto un cospicuo finanziamento da telethon e che ho invitato ad unisi a noi (il 2 Dicenbre) nella lista autismo-biologia per tenerci informati sui progressi della sua ricerca; sfortunatamento non ha ancora risposto alla mia mail...speriamo sia semplicemente un ritardo! ----------------------------------------------------------------------------- Mail ricevuto da ``apana"
From [email protected] Mon Dec 7 14:14:11 2009 Date: Mon, 7 Dec 2009 07:33:00 -0500 From: "Gail Schrimmer, PhD" <[email protected]> Reply-To: International general autism support and information. <[email protected]> To: "Undisclosed-Recipient:;"@lists.apana.org Subject: [Autism] Silenced Gene amd ASD: possible marker
Obtained from The National Institute of Mental Health Alternative Title: Silenced Gene for Social Behavior Found in Autism This news release, and an illustrative graphic, can be found at this web address < http://bit.ly/7A0UWC > Science Update December 03, 2009 Epigenetic Mark in Blood Could Serve as Biomarker for Disorder For the first time, inherited disruption of gene expression in a brain system for social behavior has been implicated in autism. NIMH grantee Margaret Pericak-Vance, Ph.D., at the University of Miami and Simon Gregory, Ph.D., at Duke University, and a multinational team of researchers found evidence for such epigenetic <http://www.genome.gov/27532724> effects on the gene for the oxytocin<http://www.nlm.nih.gov/medlineplus/news/fullstory_90892.html>receptor –– part of a brain system that mediates social behaviors disturbed in autism. The findings suggest a potential genetic biomarker for the disorder. The researchers report on their findings online October 22, 2009 in *BMC Medicine*. Background Environmentally-influenced and heritable<http://www.nimh.nih.gov/science-news/2009/gene-on-off-instructions-in herited-via-shadowy-mechanism.shtml>chemical tags called epigenetic marks regulate the mix of proteins needed to build each tissue of the body. These alterations do not change a person's DNA <http://www.genome.gov/18016863>, or genetic blueprint. However, epigenetic changes that occur from the moment sperm meets egg can alter when and where genes get turned on. Researchers are testing oxytocin as a possible treatment for social behavior disturbances in autism. Oxytocin is a hormone produced in the brain, which works through the oxytocin receptor. Previous studies had hinted at oxytocin receptor abnormalities in autism, but not at an epigenetic mechanism. The researchers first used high-tech, genome-wide techniques to search for deletions or duplications of genes in 119 people with autism from families that had multiple children with the disorder and 54 healthy controls. They then searched in brain tissue and blood samples from affected and unaffected individuals for a common type of epigenetic mark created by methylation<http://www.genome.gov/27532724#al-3>. In this process, molecules called methyl groups attach to DNA in response to an environmental trigger, preventing a gene's expression. Findings of This Study The researchers found a deletion in the oxytocin receptor gene in a person with autism and his mother, who had obsessive compulsive disorder<http://www.nimh.nih.gov/health/topics/obsessive-compulsive-disorder-oc d/index.shtml>(OCD). OCD shares with autism symptoms of repetitive behaviors. Oxytocin receptor genes were similarly silenced –– but by methylation — in a sibling with autism who lacked the deletion. That is, two separate mechanisms of gene expression regulation resulted in the same outcome — loss of oxytocin receptor expression — in the same family. Following up in blood cells and temporal cortex brain tissue of people with autism, the researchers pinpointed higher levels of methylation — about 70 percent vs. the normal 40 percent –– at an epigenomic site known to regulate the oxytocin receptor. They also found decreased expression of the receptor in the temporal cortex tissue, an area previously linked to autism. Significance Excess methylation of the oxytocin receptor could render people with autism less sensitive to the social hormone's effects. Gene expression most likely became altered in very early gestation (between fertilization and implantation), suggest the researchers. This could increase vulnerability of the oxytocin receptor gene to environmental insults during the first few weeks of pregnancy, they say. The results suggest that such epigenetic misregulation of the oxytocin receptor gene may be an important factor in the development of autism. What's Next? Since evidence of excess methylation of the oxytocin receptor gene in temporal cortex was also found in blood cells, the researchers suggest that the blood measure may be a marker, more generally, of the methylation status of the temporal cortex. So measuring the methylation status of the oxytocin receptor in blood could potentially serve as a biomarker for autism that might be used in conjunction with traditional diagnostic criteria. Drugs that target methylation might also hold promise for treatment. Reference Genomic and epigenetic evidence for oxytocin receptor deficiency in autism<http://www.ncbi.nlm.nih.gov/pubmed/19845972?itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1>. Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA. BMC Med. 2009 Oct 22;7(1):62. [Epub ahead of print]PMID: 19845972.