Genes 2 Brains 2 Mind 2 Me

Hey, why should neurons get all the adulation – you know – like an organization with 40,000 members complete with an annual fest in exotic locales?  After all, glial cells outnumber neurons many-fold and a single astrocyte can ensheath and support many hundreds of neurons.  Perhaps it may be that who gets top billing may not be so much an issue of who is more important, but just a matter of who is better known (its who you know in life that matters right?).

These were my thoughts at the start of Professor Ben A. Barres’ talk, “What do Glial Cells Do?” which I greatly enjoyed today.  One of the key things glia do, it turns out, is to help neurons form new synapses.  This can be shown by culturing astrocytes and then applying the conditioned media to rat ganglion cells – who respond by making new postsynaptic densities and also increasing the externalization of AMPA receptors.  The mediator of this process was identified as thrombospondin – a molecule that is secreted by astrocytes and binds, via its EDF-repeat domain, to a neurally expressed molecule known as alpha-2-delta-1 calcium channel subunit which signals in an integrin-like manner to initiate the formation of excitatory synapses.  A few other highlights from the talk were:

-thrombospondin is the gene which is MOST upregulated in expression when human vs. monkey brain mRNA levels are compared.

-the synapse-inducing effects of astrocytes work only in immature astrocytes and injured/reactive astrocytes, but not mature ones.

-overexpression of the alpha-2-delta-1 calcium channel subunit can induce synapse formation.

-some medications such as gabapentin/neurontin bind to the alpha-2-delta-1 calcium channel subunit and can actually interfere with the new synapse formation – red flagging these meds for use during pregnancy and in children

-there is a metal-binding domain in alpha-2-delta-1 calcium channel subunit which may – possibly – be a target for lead binding and be a reason for why small amounts of exposure to lead can lead to mental retardation

Another highlight of the talk was Professor Barres brief personal comments on the importance of gender and cultural diversity in the practice of science. I was impressed by his warm and supportive remarks to students who may be concerned about diversity and discrimination in the field of science.  Check out his wikipedia page for more.