Entorhinal cortex stimulation induces dentate gyrus neurogenesis through insulin receptor signaling.

Deep brain stimulation (DBS) has been established as a therapeutically effective method to treat pharmacological resistant neurological disorders. The molecular and cellular mechanisms underlying the beneficial effects of DBS on the brain are not yet fully understood. Beside numerous suggested mechanisms, regulation of neurogenesis is an attractive mechanism through which DBS can affect the cognitive functions. Considering the high expression of insulin receptors in hippocampus and also impaired neurogenesis in diabetic brain, the present study aimed to examine the role of insulin receptor signaling in DBS induced neurogenesis. High frequency stimulation was applied on the entorhinal cortex of rats and then neurogenesis markers in the dentate gyrus region of the hippocampus were examined using molecular and histological methods in the sham, DBS and insulin receptor antagonist-treated groups. In parallel, the changes in insulin receptor signaling in the hippocampus and spatial learning and memory performance were also assessed. DBS promoted adult hippocampal neurogenesis and facilitated the spatial memory concomitant with changes in insulin receptor signaling parameters including IR, IRS2 and GSK3ß. Application of insulin receptor antagonist attenuated the DBS-induced neurogenesis. Our data emphasize that entorhinal cortex stimulation promotes adult hippocampal neurogenesis and facilitates spatial learning and memory at least partly through insulin receptors. Notably, GSK3ß inhibition can play a major role in the downstream of insulin receptor signaling in DBS induced neurogenesis.

Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats.

Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (P<0.01). The low and high doses of tartrazine led into an increase in working and reference memory errors in acquisition and retention phases (eight-arm radial maze) compared to distilled water group (P<0.01). Additionally, the high dose of tartrazine induced a reduction in the volume of mPFC (∼13%) and its subdivision. Not only that, but the number of neurons and glial cells (∼14%) as well as the mushroom and thin spines per dendrite length declined. The length of dendrites per neuron also reduced in comparison to the distilled water group (P<0.01). Nonetheless, concomitant treatment of the rats with vitamin E plus tartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes.