مقالات پذیرفته شده در ششمین کنگره بین المللی زیست پزشکی
Optogenetics Is a New Star For The Treatment of Parkinson's
Optogenetics Is a New Star For The Treatment of Parkinson's
Fatemeh Kaviani,1,*Samaneh Dalali,2
1. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran 2. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
Introduction: Optogenetics is a technology that combines optics with genetics to induce a precise gain or loss-of-function in cells or tissue by applying light. This biological technique involves: 1) engineering a gene that must be delivered in a cell specific manner and expressed at adequate levels, 2) developing a mode to deliver light for in vitro and in vivo studies, 3) detecting the effect of optogenetics.
This light-sensitive technology has revolutionized the study of neuroscience with single-cell and millisecond precision control of neurons. Accurate spatial and temporal control is especially important to a system as complex as the nervous system, containing a network of billions of cells.
Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD is a common and slowly progressive neurodegenerative disease caused by the gradual loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). The cardinal motor symptoms of PD are tremor, rigidity, bradykinesia/akinesia and postural instability, but the clinical picture includes other motor and non-motor symptoms.
Movement disorders including Parkinson’s disease is caused by neurological dysfunction, typically resulting from the loss of a neuronal input within a circuit. Neuromodulation, specifically deep brain stimulation (DBS), has proven to be a critical development in the treatment of movement disorders. Continuing efforts aim to improve DBS techniques, both in how they exert their effects and in the efficacy of the mechanism involved in eliciting those effects. We review the benefits of cell-type specific manipulations in understanding the root cause of movement disorders and how DBS might optimally combat those causes. research employing optogenetics provides the specificity and feasibility to uncover the mechanisms that will help realize these gains in patient care.
Methods: All experiments were conducted in accordance with the guidelines of the National Institutes and the protocols approved by the The Rockefeller University Institutional Animal Care and Use Committees. Mice were housed in a 12-h light–dark cycle (lights on at 7:00) with ad libitum access to food and water. Male mice were used for all the behavioral and histological studies; both male and female mice were used for tracing studies. Mice were at 8–16 weeks old at the time of surgery. All mouse lines were in a wild-type background. The following mouse lines were used: Pitx2-Cre , Gabrr3-Cre , Sapap3 KO. The subthalamic nucleus (STN) plays a key role to control movement functions. The relationship between STN modulation with deep brain stimulation (DBS) and Parkinson's disease was investigated.
Results: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy for the motor symptoms of Parkinson's disease (PD). However, the neural elements mediating symptom relief are unclear. A previous study concluded that direct optogenetic activation of STN neurons was neither necessary nor sufficient for relief of parkinsonian symptoms.
Conclusion: The term “optogenetics” cannot be reduced to a single method or technique but can be broken down into a number of components that could be used independently of assembled in various combinations leading to a very broad spectrum of exciting therapeutic perspectives. A bright future for such applications can be foreseen. Optogenetics thus appears as a challenge well worth the substantial research effort that it stillrequires. While optogenetic stimulation is currently infeasible in human patients, opto-DBS research provides an indispensible avenue to understand the mechanisms of DBS therapeutic and adverse effects.