In a study published in the International Neurology Journal, researchers showed that cognitive deficits, such as memory problems, in a rat model of multiple sclerosis (MS) are mirrored by changes in synaptic transmission and plasticity in the hippocampus, a brain region crucial for memory processing. The findings advance the understanding of disease mechanisms affecting cognition in MS patients.
Cognitive deficits such as learning and memory dysfunction are common in MS, affecting 40 percent to 60 percent of patients. While earlier studies reported that brain inflammation might alter the generation of neuroplasticity, particularly at the synaptic level, not much is known about the mechanisms leading to such changes.
Studies also show that the hippocampus is affected by nerve cell death in MS patients. Using the well-characterized experimental autoimmune encephalomyelitis (EAE) animal model of MS, researchers at Arak University of Medical Sciences, Iran, used recordings of nerve cell activity in live rats to study the impact of disease on memory processes.
Using behavioral tests to study memory processes in EAE animals can be challenging, since these mice often have motor symptoms that might impact the outcome of such tests. Instead, information of how signals are transmitted at neuronal connections, synapses, as well as long-term potentiation — the mechanism underlying changes in synaptic strength, and hence neuronal plasticity — can be used to understand the mechanisms behind changes in memory function.
The study, “Changes in Synaptic Transmission and Long-term Potentiation Induction as a Possible Mechanism for Learning Disability in an Animal Model of Multiple Sclerosis,“ showed that the EAE mice had deficits in synaptic transmission and long-term potentiation in the hippocampus.
Further analysis, using a method called paired pulse inhibition, capable of detecting differences in effects of neurotransmitter release, showed that EAE changed the signaling by neurotransmitter GABA, the main inhibitory neurotransmitter in the brain.
The team concluded that the GABA-B receptor, one of two main receptor types for the neurotransmitter, had increased efficacy in the hippocampal region of the rats, explaining why the synaptic transmission and long-term potentiation was lower in the EAE-affected animals.