So excited to share a preprint of my second paper featuring two of my favorite things in neuroscience: astrocytes and lactate! Thread below!
https://biorxiv.org/cgi/content/short/2020.04.13.039446v1

I have to acknowledge up top my fantastic mentors, @gpetzinger and Twitter-less Michael Jakowec, who have allowed me to go off and explore projects like this. I also want to shout out our fantastic UG Tyler, who spent his lab career working with me. He’s off to @KeckMedUSC! – at USC Keck School of Medicine

This paper helps to answer a nagging question of mine. Ever since I started my (related) thesis work, a question that has been on my mind was: how much is peripheral lactate *actually* contributing to exercise-induced neuroplasticity? And how is that affecting astrocytes? – at USC Keck School of Medicine

Beautiful work by others have shown lactate-induced angiogenesis and its effect on metabolism in the brain, as well as the effect of lactate on neuronal plasticity. But, the first cells that may encounter lactate entering the brain, astrocytes, have not been looked at very much. – at USC Keck School of Medicine

We administered 10mM lactate (a physiologic approximation of plasma concentration in intensive exercise) for 1hr to primary astrocytes and found an increase in neurotropic factor (NTF) expression. This aligns with previous work in astrocyte culture and matches exercise data. – at USC Keck School of Medicine

We then used this same paradigm for 10 days in normal healthy mice walking on a treadmill, the thought being: “If we can engage motor circuitry with walking, and administer lactate to mimic exercise levels, will the brain respond like an exercised brain?” – at USC Keck School of Medicine

The answer: Yes! ...to an extent. We found increased NTF expression (along with thrombospondin) and astrocyte morphological changes *only* in the striatum (which is engaged during motor activity) but not the ectorhinal cortex (which is not engaged). – at USC Keck School of Medicine

However, we saw no effect of lactate on synaptogenesis in either region, and rotarod performance did not improve. So, NTF/ synaptogenic factor expression can go up and astrocytes can remodel in region-specific manner, and you still don’t see relevant neuroplastic change. – at USC Keck School of Medicine

There are many possible reasons for this. We believe that during exercise, peripheral lactate primes specific circuits via astrocytes for plasticity. But, without robust neuronal activity, that priming is not incorporated. Thus, lactate is not a complete “exercise pill”. – at USC Keck School of Medicine

Lactate is an important aspect of exercise, definitely not waste, and may represent a factor that links peripheral metabolism with brain circuit activity to reinforce neuroplasticity. This has expanded our thinking and reinforces that the body and brain are linked. Onward! – at USC Keck School of Medicine