An evaluation of optogenetics stimulation on alterations of microRNA 124a as neurogenesis marker in animal model of stroke

Background and Aim : Worldwide stroke is the second leading cause of mortality. Stroke has maintained its status as the largest element of disability and lethal in the last 15 years and the figures are still growing. Notably, stroke stand out as one of the prominent economic and social burden for society. Stroke is mainly provoked by a temporary and permanent blockage of the middle cerebral carotid artery and could interrupt the blood flow. Therefore, it could lead to neuronal death and sensory-motor and cognitive impairment due to decreasing in brain glucose and oxygen levels. This study was carried out for the purpose of evaluating efficiency of optogenetics as a new method in treatment of stroke, succeeding reduction of injury. Finding of this research showed that there was an improvement in the sensory-motor deficits and a significant reduction in epigenetic factors involved in the neurogenesis process through, stimulation of glutamatergic neurons of the brain striatum before stroke induction.Methods : In order to achieve the goal, lentiviruses carrying pLenti-CaMKIIa-hChR2 (H134R) - mcherry-WPRE were injected in the right striatum of rats for increasing the level of synaptic glutamate. The animals were light-stimulated 30 minutes for 6 consecutive days by using 473 nm a blue laser light 26 days after injection. The middle cerebral artery occlusion (MCAo) were induced on stroke rat model 24 h after the last light stimulation. 24 hours after reperfusion, the animals sensory-motor deficits were assessed by the neurological sensory-motor deficits index (NSS). Furthermore, the expression level of neurogenesis epigenetic marker (microRNA 124a) was evaluated using RT-qPCR technique.Results : The results showed that pretreatment with optogenetic stimulation of glutamatergic striatum neurons could increase the sensory-motor function of mice and neuronal survival in the striatum, cortex and hippocampal areas. Also, the expression levels of the miR-124a showed that modulation their specific signaling pathways leads to changes in the processes of neurogenesis and contributes to the improvement of the disease as well.Conclusion : According to the results, optogenetics pretreatment can be used as a therapeutic method for controlling and preventing further injury through the optogenetic stimulation of glutamatergic neurons of the striatum and epigenetic factors such as microRNAs.

Keywords:

Stroke , Optogenetics , miR124a , Epigenetics , Glutamate , Neurogenesis