Topic: CDKL5

Dysfunctional synaptic vesicle recycling – links to epilepsy

Accurate and synchronous neurotransmitter release is essential for brain communication and occurs when neurotransmitter-containing synaptic vesicles (SVs) fuse to release their content in response to neuronal activity. Neurotransmission is sustained by the process of SV recycling, which generates SVs locally at the presynapse. Until relatively recently it was believed that most mutations in genes that were essential for SV recycling would be incompatible with life, due to this fundamental role. However, this is not the case, with mutations in essential genes for SV fusion, retrieval and recycling identified in individuals with epilepsy. This seminar will cover our laboratory’s progress in determining how genetic mutations in people with epilepsy translate into presynaptic dysfunction and ultimately into seizure activity. The principal focus of these studies will be in vitro investigations of, 1) the biological role of these gene products and 2) how their dysfunction impacts SV recycling, using live fluorescence imaging of genetically-encoded reporters. The gene products to be discussed in more detail will be the SV protein SV2A, the protein kinase CDKL5 and the translation repressor FMRP.

CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility

CDKL5’s role in microtubule-based transport and cognitive function

Primary sensory cortices of a mouse model of CDKL5 deficiency disorder show atypical myelination

Probiotic supplementation as a potential strategy of intervention to ameliorate clinical symptoms of the CDKL5 deficiency disorder

Unusual double mutation in MECP2 and CDKL5 genes in Rett-like syndrome : Effect on genes expression and genotype phenotype correlation