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Parkinson’s Disease Model Sheds Light on Brain Circuit Therapy

QPS Neuropharmacology

Parkinson’s disease creates a number of motor and non-motor symptoms, ranging from tremors and loss of balance to depression. With such a variety of symptoms impacting patients, medical professionals are often forced to prescribe different medications to treat each symptom. But now, MIT neuroscientists have identified three distinct brain circuits that influence both motor and non-motor symptoms in Parkinson’s patients. By exploring brain circuits in a Parkinson’s disease model, the researchers may have paved the way for new, more efficient drug therapies.

graphic image of human brain with technological graphics overlaid

Understanding Parkinson’s Symptoms and Brain Circuits

Parkinson’s symptoms are often associated with the thalamus, an area of the brain that consists of several distinct regions. Many of those regions, including the parafascicular (PF) thalamus, help with movement control. Conversely, as Parkinson’s symptoms progress, patients usually exhibit degeneration in the PF thalamus. With that in mind, MIT researchers sought to explore connections between the PF thalamus and other brain regions involved in motor control and other Parkinson’s symptoms, Science Daily reports. Ultimately, the scientists found that PF thalamus neurons project to three different brain structures: the caudate putamen (CPu), the subthalamic nucleus (STN), and the nucleus accumbens (NAc). The PF thalamus neurons are connected to these structures by distinct circuits.

How Distinct Brain Circuit Functions Relate to Parkinson’s Treatment

After scientists identified the three brain structures listed above, they made a surprising discovery: The circuits connecting the PF thalamus to the structures all likely perform distinct functions:

  • The circuit that projects to the CPu was found to be involved in general movement.
  • The circuit that extends into the STN is seemingly connected to motor learning.
  • The circuit that connects the PF thalamus to the NAc was found to be linked to mood and motivation.

Exploring Circuits in a Parkinson’s Disease Model

After the researchers determined the unique function of each circuit, they used a mouse model of Parkinson’s to see if enhancing or weakening the brain circuit connections could have an impact on Parkinson’s symptoms.

Interestingly, the Parkinson’s model showed an enhanced CPu connection, which led to a decrease in movement as evidenced by engaging mouse models in an open field test. Additionally, the Parkinson’s model showed reduced motor learning with weakened STN connections, as evidenced by engaging mouse models in a standard rotarod test. Lastly, the researchers showed that the Parkinson’s model had weakened NAc connections, which led to depression-like symptoms as evidenced by the results of a number of sucrose preference tests. In the latter, the mouse models showed reduced interest in the sugar water when the NAc circuit was impeded, suggesting a depressive state.

Turning Findings into “Druggable” Treatments

The researchers’ final step was to explore molecular targets that might be “druggable.” In other words, they sought targets that could lend themselves to therapeutic drug development. Ultimately, the team honed in on thalamus cells that express different types of cholinergic receptors, which influence neuronal cell growth and survival. The scientists either blocked or activated these receptors and were successful in reversing the Parkinson’s symptoms in mouse models.

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Ultimately, the researchers hope to use knowledge gleaned from this study to develop more efficient Parkinson’s therapies. The team has a long way to go; the types of neurons that they identified in the mouse models’ brains are also found in primate brains, but researchers still need to explore the behavior of similar circuits in human brains. Still, this study could prove extremely promising after further exploration.

QPS Neuropharmacology is a division of QPS, a GLP/GCP-compliant contract research organization (CRO) delivering the highest grade of discovery, preclinical, and clinical drug development services since 1995. QPS Neuropharmacology focuses on preclinical studies related to central nervous system (CNS) diseases, rare diseases, and mental disorders. With highly predictive disease models available on site and unparalleled preclinical experience, QPS Neuropharmacology can handle most CNS drug development needs for biopharmaceutical companies of all sizes. To study Parkinson’s disease, QPS Neuropharmacology offers several in vitro and in vivo models and corresponding motor tests as well as ex vivo analysis tools. For more information about QPS visit www.qps.com, and for more information about QPS Neuropharmacology, visit www.qpsneuro.com.