My last few blog posts on Science Over a Cuppa have focused on some of our recent genomics work involving neuronal immaturity in autism [1, 2]. Specifically, I’ve talked about how the impairment of autism-risk genes may predispose towards disturbances to the maturation of neurons in the autistic brain.
For today’s blog post I’m reviving an oldy-but-goody, which is highly relevant to our recent findings and that of other researchers, such as Ben-Ari’s work on excitatory GABA in autism . Back in 2012, Gandal et al. published a paper titled, Measuring the Maturity of the Fast-spiking Interneuron Transcriptional Program in Autism, Schizophrenia, and Bipolar Disorder, which is basically a long way of saying that the maturation of inhibitory neurons are suppressed in autism, schizophrenia, and bipolar.
Two examples of interneurons: the parvalbumin-positive (Pv+) basket cell, and the chandelier cell. Both synapse onto the excitatory pyramidal cell and help to regulate its activity.
What the team did was compare normal gene expression profiles of the fast-spiking parvalbumin-expressing GABAergic interneurons, a specific subset of inhibitory cells that provide for synaptic inhibition of excitatory pyramidal cells, to expression of those same genes in autism, schizophrenia, and bipolar. They found that expression profiles in these conditions reflected a more immature state as compared to control tissues. In addition, levels of parvalbumin were markedly reduced in the conditions, suggesting that the maturation of the fast-spiking parvalbumin-positive interneurons is particularly affected. What this may mean is that inhibition of the pyramidal cells they normally regulate may be impaired, potentially leading to hyperexcitability, a theme well known in the autism literature.
Figure from Gandal et al. (2012). Panels a-c show the maturation index, reflective of gene profiles relevant to interneuronal maturation across autism, schizophrenia, and bipolar. Panels d-f show parvalbumin expression levels in the three conditions.
Our team is currently collaborating in a study investigating GABAergic labeling in brains of autistics, including idiopathic autism as well as a form of syndromic autism. It’ll be interesting to see if our immunohistochemical results match with the molecular data presented by Gandal et al. If they do, this could be one more step towards understanding how disturbances to neuronal maturation may be involved in autism, not just targeting the excitatory component of the human brain, but also the inhibitory one. Hopefully more to come in future, stay tuned…