Question And Answer Session

PARTICIPANT: I was curious about your data with the monkey cortex.

DR. MOFFETT: Yes.

PARTICIPANT: Are you not finding NAAG in pyramidal neurons?

DR. MOFFETT: Yes, we do in the monkey. Those are all pyramidal cells in layer 5, these large ones. It was only in rat cortex where we did not see NAAG in pyramidal cells.

PARTICIPANT: You showed a monkey cortex, where you showed the comparison to GAD67.

DR. MOFFETT: Yes. Here are some layer V pyramidal cells. And these pyramidal cells were chopped off, and are not visible in this particular 20-micron-thick section, but you can still clearly see that their apical dendrites are heavily labeled. So that's just a particular place where we only picked up two in that spot.

PARTICIPANT: You see it in pyramidal neurons in other layers, also?

DR. MOFFETT: Yes.

SESSION CO-CHAIR COYLE: That raises an interesting question in terms of animal models. We may potentially get misled about the salience of NAAG in cognitive processing because of the under representation of NAAG in mouse/rodent pyramidal neurons.

DR. MOFFETT: Yes. But in terms of non-cortical NAAG expression, the rodent brain is very similar to the situation in carnivores and primates. Even in rat cortex, NAAG immunoreactivity in non-pyramidal neurons is virtually identical to that in primates.

The one other question - we can't really answer too many functional questions with structural studies like this - but the one question that keeps coming back to me is that we have extremely high levels of NAA in virtually all neurons, especially in pyramidal neurons, but there is no deacetylase known that can metabolize NAA in neurons. So that's a question we still have to figure out. Why is there so much NAA in a cell type that cannot further metabolize it?

SESSION CO-CHAIR COYLE: I think you find that in terms of GABAergic neurons in particular, when you raise the question of what is colocalization all about; GABA is certainly an inhibitory neurotransmitter, plus NAAG activating mGluR3; Barbara Wroblewska has shown that, which further down-regulates excitatory neurotransmission, so that colocalization is coherent.

DR. MOFFETT: Yes.

Dr. WEINBERGER: It's also even beyond that level of coherence because mGluR3 is a heteroreceptor that is also found on all of these other neurotransmitter terminals. So there may actually be a local circuit of NAAG regulation of mGluR3 acting at various heteroreceptor terminals.

DR. MOFFETT: I did not focus on it, but you can quite clearly see examples of synaptic-like contacts on dendrites, where there are no obvious axons coming in. And to me, this suggests that these might be presynaptic on a dendrite. In other words, NAAG is being secreted from presynaptic sites on dendrites, which would also be unusual.

SESSION CO-CHAIR BURLINA: Other questions?

PARTICIPANT: Is there anything known about the localization of NALADase?

DR. MOFFETT: Primarily astrocyte, isn't it?

SESSION CO-CHAIR COYLE: Yes, it's in astrocytes, but it looks like it's on the end feet. When you make synaptosomal preparations you get NALADase is enriched in the synaptosomes, which could mislead you to think it is in nerve terminals, but those preparations also contain astrocyte end feet.

DR. MOFFETT: End feet, yes.

SESSION CO-CHAIR COYLE: Thank you very much.

DR. MOFFETT: Thank you.

Was this article helpful?

0 0

Post a comment