Hi,
last year there was an article in Molecular Brain by Jae-Young Koh and colleagues about BDNF and shank regulation in ASD. They proposed the novel hypothesis that zinc-metalloprotease-BDNF axis in the forebrain plays important role in the development of hyperconnectivity and megalencephaly in ASD.
All in all, some animal models of ASD show increased levels of BDNF so if somehow shank could increase BDNF it could be involved in pathology of ASD. It is known that shank plays important role in synaptic plasticity so it sure is potential etiopathogenic crossroad. It is also shown that insufficiency of Shank3 causes Phelan-McDermid syndrome (mental retardation and autistic behavior). The way BDNF and shank are interconnected is indirectly through synaptic zinc. Synaptic zinc upregulates BDNF. BDNF injection upregulates MMP so there could be some kind of positive feedback loop which is important since Zn might directly upreglate MMP. Also, various stimuli such as an infection or environmental toxins can stimulate release of zinc in synapse (environmental toxins such as thimerosal can directly activate microglial and neuronal BDNF/TrkB). Shanks may also be controlled by synapttic zinc levels. It is proposed that synaptic zinc activates shank and that shank regulates presynaptic zinc through negative feedback loop. If synapses are deficient in shank there is missing negative part of the loop that doesn't allow presynaptic zinc to be to high. So mutations in shank could lead to high presynaptic zinc which causes excessive metalloprotease activation and upregulation of BDNF at the synapse. This could lead to hyperconnectivity and increased number of synapses but the synapses would still be dysfunctional (hyperconnectivity and large brain size are common in young idiopathic ASD patients). I believe there is a lot of other explanations but this one is for sure interesting.
I'll attach the paper. I hope this was helpful.
Best regards,
Jan Homolak
Hai Jan!!
Thank you for your post.. really it is an useful information..
Dear Govindaraj,
I send you one article. In this article you will see for BDNF in module "Neuronal plasticity and neurotrophic factors: the key to the case" I hope this was helpful.
Sincerely,
Kostas Mantzikos
http://www.encephalos.gr/48-3-01e.htm
I send you one article with title "Genetics of autism spectrum disorder & BDNF gene" by
Usha P. Dave
Dear Kostas!!!
Thank you so much for your help.. this will really help me a lot to understand the role of BDNF in autism.. but i didn't get that full paper..
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