Protein expressions in the rat hippocampus following deep brain stimulation of the fornix area

2015  -  Toronto, ON, CA

Organizations

University Health Network

Supervising Advisor: Dr. Andres Lozano

Project summary:

Deep brain stimulation (DBS) refers to the therapeutic delivery of electrical current through implanted electrodes in precisely targeted areas of the brain. It is estimated that over 100,000 patients worldwide have been implanted with DBS systems, with the rate of annual accrual increasing. DBS has proven effective in treating a range of neurological disorders including Parkinson’s disease, essential tremor, dystonia, pain and psychiatric illness. Recently, beneficial effects of DBS have been reported for memory enhancement in rodents and humans. Our group was the first to perform a study in patients with Alzheimer’s disease (AD) investigating the safety of DBS targeting the limbic system as potential treatment for dementia/cognitive impairment. In this trial, six patients with AD were treated by implantation of DBS electrodes in the vicinity of the fornix and were treated for 12 months with DBS. Follow-up PET scan studies at one year revealed increases in cortical glucose metabolism that were correlated with improved cognitive measures in a subset of these patients. Despite the widespread and successful use of DBS in patients, the exact mechanisms of action for DBS in general and specifically for forniceal stimulation on the neuronal activity of the hippocampus remain unknown.

In my current research, I am investigating the effects of forniceal DBS on the modulation of protein expression in the rat hippocampus. Our preliminary data show that forniceal DBS increases cFos level in the hippocampus,suggesting that forniceal stimulation lead to sustained hippocampal activation.

Final summary:

Deep brain stimulation (DBS) refers to the therapeutic delivery of electrical current through implanted electrodes in precisely targeted areas of the brain. It is estimated that over 100,000 patients worldwide have been implanted with DBS systems, with the rate of annual accrual increasing. DBS has proven effective in treating a range of neurological disorders including Parkinson’s disease, essential tremor, dystonia, pain and psychiatric illness. Recently, beneficial effects of DBS have been reported for memory enhancement in rodents [6-9] and humans.  Our group was the first to perform a study in patients with Alzheimer’s disease (AD) investigating the safety of DBS targeting the limbic system as a potential treatment for dementia/cognitive impairment. In this trial, six patients with AD were treated by implantation of DBS electrodes in the vicinity of the fornix and were treated for 12 months with DBS. Follow-up PET scan studies at one year revealed increases in cortical glucose metabolism that were correlated with improved cognitive measures in a subset of these patients. Despite the widespread and successful use of DBS in patients, the exact mechanisms of action for DBS in general and specifically for forniceal stimulation on the neuronal activity of the hippocampus remain unknown.

In this past year, I investigated the effects of forniceal DBS on the modulation of protein expression in the rat hippocampus. We first showed that forniceal DBS increases cFos level in the hippocampus, suggesting that forniceal stimulation lead to sustained hippocampal activation. Forniceal DBS triggers hippocampal activity which rapidly modulates the expression of neurotrophic factors and markers of synaptic plasticity known to play key roles in memory processing. These findings could have significant clinical implications for individuals suffering from memory impairments.