Lindgren Continues Research with New NIH Grant

Clark Lindgren, professor of biology at Grinnell College, was recently awarded a $419,767 grant from the National Institutes of Health through their Academic Research Enhancement Award program. A renewal of a 2010 AREA grant, the award will allow Lindgren to continue studying chemical synapses beginning in April 2014.

Chemical synapses are places where nerve cells communicate with other nerve cells, or muscle cells, or gland cells. Lindgren will examine an example of a model synapse located between the nerve and the muscle, called the neuromuscular junction.

“In our lab we believe that the neuromuscular junction is the most important synapse in animals,” Lindgren stated. “You can have the best brain in the world, the most precise sensory mechanisms that allow you to spot danger or potential rewardd—but if you can’t get your muscles to move, you are in serious trouble.”

Lindgren’s research has three main goals:

— First is to understand if chemicals called endocannabinoids function at the mammalian neuromuscular junction. Endocannabinoids are endogenously produced chemicals that act like tetrahydrocannabinol, the active ingredient in marijuana.

— Second, the research plans to examine whether non-neuronal brain cells, called glial cells, play a direct role in synaptic transmission at the neuromuscular junction. Glial cells are known to provide nutrients to neurons, removing debris that accumulates in the extra-cellular space. They also play an important role in early development, directing neurons to their proper targets.

“Traditionally, neuroscientists assumed glial cells performed ‘blue collar’ jobs,” said Lindgren. “They were the cafeteria workers, the garbage collectors, the daycare workers, and so forth.… What we are just now learning is that glial cells are much more involved in transmitting signals throughout the nervous system, that is, the nitty-gritty functions that we have previously only associated with neurons,” he added.

— Third, the research explores why neuromuscular junctions have receptors for the chemical glutamate. In a previous paper, Lindgren found that a dipeptide called N-acetylaspartylglutamate (NAAG) is found in the nerve terminal, and it activates a certain glutamate receptor.

“What happens is that NAAG, when it first gets released, can activate one type of glutamate receptor, but after it is released an extracellular enzyme coverts it to glutamate, which activates a different type of receptor. So the third aim is to follow up on that rather complicated scenario.” Lindgren stated.

A lab technician, Steve Ryan, and two students currently work with Lindgren. Kaya Matson ’14 and Erica Kwiatkowski ’15 are doing projects related to the previous grant. Lindgren is currently in the process of selecting four new summer students.

Lindgren’s ongoing research has clinical health implications. Legalization of marijuana means that there are more people who are going to be taking chemicals that will potentially negatively interact with the endocannabinoid receptors. Further, endocannabinoid receptors have been channeled in therapeutic ways – in weight loss and smoking cessation, for example. However, Lindgren’s research suggests that such methods would compromise neuromuscular endurance. Additionally, Lindgren’s research also has the potential to contribute to understanding how neuromuscular junctions start to deteriorate over time, assisting in the literature on diseases of the neuromuscular junction such as Duchenne Muscular Dystrophy.