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The Harold L. Dorris Neurological Research Center
The Harold Dorris Neurological
Research Center, founded in 1999 with a $10 million commitment by Helen L.
Dorris through the Harold L. Dorris Foundation, has attracted an international
cadre of scientists who conduct research into neurological disorders from such
disciplines as neurology, immunology, chemistry, molecular biology, and
endocrinology.
One area of research seeks to
determine which genes are involved in thermoregulation. What makes a person hot
and feverish when they are sick? Despite being among the most common conditions
since the origin of humankind, fever and thermoregulation are still not
completely understood.
Another area under investigation
involves a regulatory gene that controls the expression of other genes within
neuronal cells. This "transcription factor," called c-fos, binds with other
proteins and to DNA, stimulating the expression of particular genes and
inhibiting the expression of others late in a neuron's development. Investigators
in the center are determining the pathways through which c-fos is controlled.
Another group investigates
hippocampal excitability--the activation of neurons in the hippocampus, which is
a prerequisite for learning and memory. The hippocampus is a ridge of tissue in
the brain that scientists think is responsible for many of the chemical
processes that are important for forming and retaining memories. These are the
basic processes of cognition.
Investigators at the center have a
made a model that overproduces a natural substance in the brain that is
important in hippocampal excitability. The neuropeptide galanin exists in
hippocampus neurons and is released, along with the neurotransmitter
acetylcholine, into the gaps, or synapses, between two neurons during the
signaling from one neuron to another during cognitive processes.
Galanin is a neuropeptide that is
widespread throughout the central and peripheral nervous systems. It has been
found to influence several physiological processes, and these include
cognition, memory, the release of various neurotransmitters and hormones, and
the regulation of motility, digestion, and sexual behavior.
Galanin is also a growth-promoting
molecule, and its local expression is required for the growth of certain neurons.
In Alzheimer's disease, galanin is overexpressed in the basal forebrain.
Moreover, as Alzheimer's disease wipes out many of the cholinergic neurons of
the hippocampus, those that survive show elevated expression of galanin. The
center hopes to make use of this information to determine how to restore the
survival and function of cholinergic activity in Alzheimer's patients, which is
a promising way of promoting cognitive improvement.
Another group studies models of
schizophrenia, a puzzling psychotic illness that involves multiple genes and
many environmental factors. Also puzzling is the fact that while initiation of
schizophrenia may begin during the formation of the laminar organization of the
brain's neocortex and prefrontal cortex during early development, in general,
serious symptoms do not appear until adolescence or early adulthood.
Although there is limited
information about the origin and underlying neural mechanisms of schizophrenia,
there are laboratory models with neurodevelopmental abnormalities that mimic
aspects of the clinical condition. Investigators use these models to study how
neurodevelopmental abnormalities relate to behavioral changes. They hope
eventually to develop models for studying schizophrenia that faithfully
reproduce both the pathological processes and phenomenology associated with the
disease in order to predict a patient's responsiveness to antipsychotic drugs.
Another model under investigation
involves an immune system regulatory molecule, or cytokine, known as interleukin
18 (IL-18). IL-18, which has anti-tumor and antimicrobial action, is produced
by a variety of cell types and tissues, and plays, a role in mediating
inflammation associated with tissue damage, autoimmune diseases, and allergic
reactions. High levels of IL-18 have also been found to be associated with
schizophrenia.
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