Graduate Studies Faculty

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Detlev Boison, Ph.D.

Adjunct Professor
Admin Unit: SOM-Neurology Department
Phone: (503) 413-1754
Office: Legacy Research Institute
Neuroscience Graduate Program
Research Interests:
homeostatic regulation of brain activity, adenosine, glycine, epilepsy, injury, schizophrenia, stem cells, gene therapy, transgenic rodent models, therapy development, local drug delivery, ketogenic diet. » Click here for more about Dr. Boison's research » PubMed Listing
Preceptor Rotations
Dr. Boison has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Boison is available as a mentor for 2016-2017.

The focus of my work is the brain’s endogenous anticonvulsant and neuroprotectant adenosine. We try to understand how adenosine function and dysfunction contributes to normal and pathological brain function, respectively, and to translate these findings into novel therapeutic approaches. We study adenosine-related physiological and pathophysiological mechanisms in rodent models of disease and in mice with engineered mutations in adenosine metabolism or signaling. Bioengineered polymers, stem cell therapies, and gene therapies are used to afford therapeutic augmentation of the adenosine system. We apply these tools to study disease mechanisms and treatment options in epilepsy, traumatic brain injury, stroke, and schizophrenia.

The Adenosine Kinase Hypothesis of Epileptogenesis
Research from several laboratories suggests that epilepsy is a disease of astrocyte dysfunction and challenges the neurocentric dogma in epilepsy research. Identification of the astrocyte as a new therapeutic target for epilepsy therapy is important, since current antiepileptic drugs, that all act by modifying the function of neurons, fail in about one third of all patients with epilepsy. The brain of individuals who suffer from epilepsy is characterized by astrogliosis. Little is known about the mechanisms that link astrogliosis to neuronal dysfunction, but it is hoped that identifying these mechanisms could lead to new possibilities for therapeutic intervention. Using a mouse model of focal epileptogenesis whereby injection of the chemical kainic acid (KA) into the amygdala restricts astrogliosis and epileptogenesis to the CA3 region of the hippocampus, we have shown that adenosine kinase (ADK) expressed by astrocytes is a key molecular link between astrogliosis and neuronal dysfunction. Expression of ADK was shown to be upregulated only in the CA3, and spontaneous focal electroencephalographic seizures were also restricted to this region of the brain. Consistent with a central role for ADK in neuronal dysfunction, transgenic expression of ADK in the CA3 induced spontaneous seizures in this region of the brain, and mice in which expression of ADK was reduced in the forebrain were resistant to KA-induced epileptogenesis. Furthermore, ADK-deficient ES cell-derived neural progenitor grafts suppressed astrogliosis, ADK upregulation, and seizures when implanted after KA administration. We therefore suggest that increased expression of ADK might predict epileptogenesis and that ADK-based therapeutic strategies might provide a new approach for the treatment of individuals with epilepsy.

Focal Adenosine-Augmentation Therapies to Treat Epilepsy
Research from our lab has demonstrated that deficiencies in the brain's own adenosine-based seizure control system contribute to seizure generation. Consequently, reconstitution of adenosinergic neuromodulation constitutes a rational approach for seizure control. Therefore, focal adenosine augmentation therapies (AATs) have significant potential for antiepileptic and disease modifying therapy. Due to systemic side effects of adenosine focal adenosine augmentation - ideally targeted to an epileptic focus - becomes a therapeutic necessity. This has experimentally been achieved in kindled seizure models as well as in post status epilepticus models of spontaneous recurrent seizures using four different therapeutic strategies: (i) Polymer-based brain implants that were loaded with adenosine; (ii) Brain implants comprised of cells engineered to release adenosine and embedded in a cell-encapsulation device; (iii) Direct transplantation of stem cells engineered to release adenosine; and (iv) Knockdown of ADK in vivo using viral gene therapy vectors. To meet the therapeutic goal of focal adenosine augmentation, genetic disruption of the adenosine metabolizing enzyme adenosine kinase (ADK) in rodent and human cells in vitro (ex vivo gene therapy) or directly in vivo (in vivo gene therapy) was used as a molecular strategy to induce focal adenosine augmentation, which demonstrated potent antiepileptic and neuroprotective properties.

The adenosine hypothesis of schizophrenia
Schizophrenia (SZ) is a debilitating mental illness with tremendous human, social and financial costs to society. Unfortunately, existing treatments are unsatisfactory and current development remains stagnant due to poor understanding of the biological bases of the disease. Two perspectives have emphasized disturbances in two neurochemical messengers in the brain -dopamine and glutamate, in relation to disparate SZ- symptoms. In our studies we examine a third messenger -adenosine, as a potential link uniting the dopamine and glutamate hypotheses of SZ. Adenosine can regulate both dopamine and glutamate neurotransmission via receptors with opposing actions (A1 vs. A2A adenosine receptors). Adenosine is therefore uniquely positioned as an upstream coordinator/regulator between these two neurotransmitter systems. Hence, adenosine-based treatment may be an attractive alternative with dual corrective actions on the glutamate and dopamine systems, thereby achieving effective control over selected SZ symptoms. Our central hypothesis is that subtle disturbances in adenosinergic neuromodulation can give rise to selected behavioral endophenotypes implicated in SZ; thus corresponding corrective interventions targeting at the ADO system should confer therapeutic potential against such SZ endophenotypes, and thereby validate our hypothesis.