 |
 |
Harold L. Dorris
Neurological Research Institute
About
Alzheimer’s disease, depression, and schizophrenia are major illnesses affecting millions of people in our society. The largest study of memory performance during aging involved the examination of the brains of nuns, several hundred of whom were followed closely by their fellow nuns, as well as by a clinical psychologist during life and donated their brains post mortem for evaluation. This study showed that the most important anatomical brain difference between those who died with Alzheimer’s disease from those who did not, was in the number of surviving galaninergic neurons. Nuns with a larger number of galaninergic neurons at the time of death had better cognitive function. The Bartfai laboratory is one of the key sites of work on galanin, this important neuropeptide, and through the past 18 years has developed genetic and pharmacological tools for the study of the effects of galanin on hippocampal neurons involved in memory function and neuronal survival. A large number of scientists at The Harold L. Dorris Neurological Research Institute study galanin signaling in the brain, and the effects of galanin on LTP and memory tasks in brain preparations and in animals. Among their recent results is the development of the first galanin receptor agonist that can be given systemically and which reaches the brain, changing the seizure threshold, thus slowing epileptic seizures, and also affecting learning and memory. Recently, they have shown that galanin, acting at the type--2 receptor, exerts a neuroprotective effect. Thus agonists of this galanin receptor are candidates for slowing disease progression in Alzheimer’s disease.
Schizophrenia is a devastating psychiatric disorder that affects 1% of the world’s population. Dr. M. Margarita Behrens and her group works on new approaches focusing on the treatment of this disease, based on the understanding that the cognitive aspects of the disease are as important as the hallucinations and other, so called positive symptoms, addressed by present antipsychotic treatments. Her approach is based on the theory of lowered glutamatergic signaling in certain parts of the brain, including the frontal cortex, and on defining mechanisms and agents to enhance the effects of glutamate at the NMDA receptors.
Depression is widespread in our society as well, exacting a heavy toll. According to estimates from the National Institute of Mental Health, about 1 of every 10 American adults has some major form of depression. Dr. Bruno Conti and his group works on the problem of finding a faster acting antidepressant than the presently used Prozac and its competitor drugs. He is also comparing the clinically well proven effects of sleep deprivation and electroconvulsive shock. These are drastic treatments that are used only sparsely, but which are fast in their action and very effective when suicide risk is high. He and his colleagues, in collaboration with Novartis scientists, have mapped transcriptional changes caused in different brain regions by these treatments. These gene chipping experiments are being followed by imaging the gene products and examining their function and alterations during antidepressant treatments.
Another area of active research at The Harold L. Dorris Neurological Research Institute involves determining which proteins in the warm sensitive neurons of the hypothalamus are involved in thermoregulation. What makes a person hot and feverish when he or she is sick? Even though fever is one of the most common conditions since the origin of humankind, the pathways involved and the mechanisms that underlie fever and thermoregulation are still not completely understood, but it is clear that these are important for understanding inflammatory mechanisms. Research in this area will have an impact on the treatment of hot flashes.
Treatment for these conditions requires an understanding of their underpinnings, and this need is addressed by The Harold L. Dorris Neurological Research Institute. Founded in 1999, as the result of a $10 million long--term commitment by Helen L. Dorris through The Harold L. Dorris Foundation, named in her brother’s honor, the Institute has attracted an international cadre of scientists from such disciplines as neurology, immunology, chemistry, molecular biology, and endocrinology to study neurological disorders.
(From TSRI Endeavor - Volume Three, Number One)
|
|
