A new study led by scientists from the Korean Institute of Science (South Korea) and the Lee Kong Chian School of Medicine (Singapore) “knocks down three decades of consensus” on the causes of Parkinson’s disease symptoms. What is behind this chronic disease? Generally speaking, it is known to be caused by insufficient levels of the neurotransmitter dopamine, but precisely what causes the motor problems (such as tremors or stiffness) that characterize this low-dopamine condition is unknown.
Voluntary movement is regulated by the basal ganglia of the brain; These modulate locomotion by activating (excitatory signals) and suppressing movement (inhibitory signals). Its balance is equivalent to our movements being smooth.
Researchers have long believed that a lack of dopamine causes motor dysfunction in Parkinson’s . However, the study published in the journal Neuron challenges this belief by employing cutting-edge technology: optogenetics.
Using optogenetics – a technique in which neurons are genetically modified to respond to light, allowing researchers to track and control the behavior of neurons – the scientists stimulated inhibitory inputs from the basal ganglia of a group. of rodents; that is, they intensified the motor suppression instructions. This caused thalamic neurons – involved in motor control – to become hyperactive .
This hyperactivity appeared to cause muscle stiffness and twitching in rodents, the hallmark of Parkinson’s disease.
As the authors explain, this is a phenomenon called “rebound firing,” which appears to be triggered by the intensification of inhibitory inputs from the basal ganglia. However, in mice with abnormally low dopamine levels but in which the hyperactivity of thalamic neurons was suppressed by optogenetics, the mice showed normal movement and no symptoms of Parkinson’s.
“In a low dopamine state, the number of [thalamic ventrolateral] neurons showing post-inhibitory firing increases, while the number of active neurons is reduced [by inhibition of the basal ganglia], effectively preventing motor symptoms of the Parkinson’s, “the authors explain.
“This study overturns three decades of consensus on the origin of Parkinson’s symptoms,” says Daesoo Kim, co-author of the work.
“The therapeutic implications of this study for treating Parkinson’s symptoms are profound, and it may soon be possible to remedy movement disorders without using L-Dopa, a precursor to dopamine,” comments Jeongjin Kim, another of the authors.
“Our results are a breakthrough, both in understanding how the brain normally controls our body’s movement and how this control goes awry during Parkinson’s disease and disorders related to dopamine deficiency,” concludes George Augustine of the Lee School of Medicine. Kong Chian from Singapore.
References: Jeongjin Kim, Youngsoo Kim, Ryuichi Nakajima, Anna Shin, Minju Jeong, Ah Hyung Park, Yongcheol Jeong, Seonmi Jo, Seungkyoung Yang, Hosung Park, Sung-Hwan Cho, Kwang-Hyun Cho, Insop Shim, Jae Hoon Chung, Se-Bum Paik, George J. Augustine, Daesoo Kim
Inhibitory Basal Ganglia Inputs Induce Excitatory Motor Signals in the Thalamus. Neuron 2017. dx.doi.org/10.1016/j.neuron.2017.08.028
