HMB200H1 Lecture Notes - Lecture 11: Shank3, Mecp2, Gaba Receptor
Document Summary
Modeling asd neurobiology: arg(cid:1008)(cid:1009)1 c(cid:455)s(cid:1008)(cid:1009)1 (cid:894)r(cid:1008)(cid:1009)1c(cid:895) su(cid:271)stitutio(cid:374) i(cid:374) nlg(cid:1007) alters a (cid:272)o(cid:374)ser(cid:448)ed residue i(cid:374) s(cid:449)edish fa(cid:373)il(cid:455) that (cid:449)as li(cid:374)ked to asd. The mouse model showed r451c enhances gaba signalling (greater inhibition in adult but greater depolarization in animals) Shank is a key protein in postsynaptic scaffold at glu synapses which interacts with synaptic proteins including nxn-nlgn complexes. Shank3 mutant display asd like behaviours: neuroph(cid:455)siolog(cid:455) is redu(cid:272)ed e(cid:454)(cid:272)itator(cid:455) tra(cid:374)s(cid:373)issio(cid:374) at s(cid:455)(cid:374)apse asd phe(cid:374)ot(cid:455)pes i(cid:374) (cid:373)i(cid:272)e. Shank3 ko = increased grooming, reduced time in open arm and antisocial: mutations in x-linked mecp2 gene causes retts syndrome; asd; and several neurodevelopmental disorders, mecp2 is found in gaba neurons (not only gaba neurons) Loss of mecp2 in gaba neurons: reduced inhibitory signalling on presynaptic side but normal. Conclusion: reduced gaba nt release: asd seems to be imbalance of excitation or inhibition in either direction (enhanced gaba signalling or inhibition of gaba signalling, this contribute to asd being a spectrum)
