Study of gliogenesis and neurochemistry underlying psychomotor retardation induced by chronic stress and the therapeutic approach of motor training in reversing the adverse effects

Abstract

Psychomotor retardation has been regarded as one of the key symptoms found in depressive patients which alteration in gross activities, fine movements and increased in latency of response have been observed in these patients. Motor training was previously shown could improve the motor performance impariement inpatients. Recently, a close relationship between the alteration of the white matter integrity and the symptom has been reported in human studies suggesting the possible involvement of oligodendrocyte function and myelination in the symptom.

Layer I within the neocortex is cell-sparse and highly charaterized with presence of high density of myelinated axons such that it has been rarely investigated about their functional role and their cellular changes under various conditions. However, layer I of the cerebral cortex has been previously suggested to be the novel neurogenic site found in rodents under pathological conditions. Collectively, our core investigation in this study is to determine if stress could alter any neurogenesisor gliogenesis within the layer I of the motor representative region and to determine if the symptom could be alleviated by motor training via modification of the cellular integrity within the layer I of the motor cortex.

Sprague-Dawley were treated either with vehicle or corticosterone(stress hormone in rodents), and were assigned into groups with or without rotarod training continuously for 14 days. Bromodeoxyuridine (BrdU) were injected during the last 3 days or first 3 days of the treatment for tracing the proliferating cells and determine the survival of the BrdU-labeled cells respectively within the motor cortex. Our results showed that corticosterone induced both depression-like behaviors and motor deficit in animals whereas these symptoms could be alleviated by rotarod training. In association with the behavioral changes, the BrdU positive cells were found to be altered obviously in the layer I of the motor cortex only under stress whereas this decrease could be reversed by rotarod training. These BrdU positive cells were mostly co-expressed with neuronal-glia antigen-2 (NG2) (an oligodendrocyte precursor cells marker), the percentage of co-expression is enhanced by rotarod training and altered by stress. We have further found that stress could reduce expression of myelin-related proteins within layer I by densitometry which the level of myelin-related proteins was increased by rotarod training.

Furthermore, we have found that these proliferating cells were involved in the neural circuitry of motor activity which these cells were activated during the rotarod training under both control and stress condition as they expressed c-fos and egr-1(immediate-early gene markers) upon stimulation. However, the activation level was found to be lowered under stress. We have applied anti-mitotic drug for blocking these proliferating cells to determine their functional role which the rotarod effects were abolished and the motor performance was impaired. These findings may not only provide the importance of the cellular changes within the layer I of the cerebral cortex in relation with psychiatric illness which has not been previously reported, but also provide a new insight for other illnesses which share similar symptomatology.