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[Introduction]
[Agenda] [Abstracts]
[Recommendations]
[Roster]
Introduction
In collaboration with Dr. Jonathan Pollock of the Division of Neurobiology
and Behavioral Research (DNBR) and Dr. Joe Frascella of the Division of
Treatment Research and Development (DTRD), Dr. Jag Khalsa of NIDA's Center
on AIDS and Other Medical Consequences of Drug Abuse (CAMCODA) presented
a mini-symposium on Substance Abuse and Neuropsychiatric Disorders at
the International Workshop on Brain Banking, March 11-12, 2002. The workshop
was organized by Dr. Piotr Kozlowski, a neuropathologist at the National
Institute of Neurological Disorders and Stroke (NINDS), (currently Director,
New York State Institute for Basic Research in Developmental Disabilities),
and co-sponsored by the National Institute on Drug Abuse, and National
Institute on Aging of the National Institutes of Health (NIH). More than
60 neuroscientists, neurologists, and neuropathologists presented outstanding
research and suggestions for the establishment of brain tissue respositories
("Brain Banks") in the United States and abroad. The mini-symposium participants
discussed issues relevant to drug abuse and HIV-related neuropsychiatric
and neurological complications and made recommendations for future research
(see under RECOMMENDATIONS). The abstracts are being published as a supplement
to the Journal of Pathology and Experimental Neurology and a summary of
the workshop proceedings is being published elsewhere. The information
relevant to drug abuse and HIV infection is summarized below.
In general the participants discussed issues of the need and type of
tissue collection, storage, and distribution/shipping. Based on their
experiences, they stated that tissues from discrete areas of the brain
and every stage of disease are needed for the understanding of pathophysiology
of, e.g., Alzheimer's, Parkinson's, schizophrenia or other diseases. A
careful dissection of anatomically distinct small regions of the brain
is critically important, for example, for the best use of new and sensitive
techniques such as massively parallel signature sequencing (MPSS). Further,
new techniques also are needed for separating individual cell types since
mRNA shows different rates of degradation in different cell populations.
But it is also important to note that diseases influenced by a large variety
of susceptible genes may require large sample populations. On the subject
of tissue collection, it is critical to maintain an excellent symbiotic
and collaborative relationship with the local Medical Examiner's (ME)
Office and MEs elsewhere in order to collect the post-mortem tissue (whole
brain or specific brain areas) in a timely manner and after proper and
ethnically sensitive consent from the appropriate relative(s) has been
obtained. It may be necessary to educate the ethnically sensitive public
in maximizing access to post-mortem tissue for brain research. Publicity
may also help in enlisting "control" cases, e.g., brains of non-cognitively
impaired famous people following sudden death. It is also essential to
use standardized methods of tissue harvesting (timing of collection),
preparation, and preservation across as many as ME offices and Brain Banks
in the US and abroad. Access to ME cases must be faciliated not just for
control cases but because sudden deaths represent, and include, important
fields of inquiry, e.g., drug abuse, suicide, neuropsychiatric disorders.
On the subject of storage of brain tissue, it is important to note that
a pH of <6 is hypoxic while a pH of >6.4 is considered a better
indicator of postmortem (PM) tissue preservation. On the other hand, a
wide range of postmortem pH (6.5-7.2) and brain tissue storage has minimal
effect on mRNA preservation. Therefore, researchers should be trained
in the art of collecting and storing brain tissue, brain tissue handling
protocols used by domestic and international brain tissue repositories
("Brain Banks"), and sensitivities and limitations of the current methodology,
e.g, microarray technology. Further, in the current genomics age, since
there are 30,000-40,000 genes, 100,000 proteins, and 50-70% are expressed
in the brain, the human brain tissue is essential for not only determining
location and/or function, but also for detecting splice variants. Other
critical elements discussed are further elaborated below.
To study the neurological and neuropsychiatric effects of drugs of abuse
and or HIV infection, it is important to obtain accurate history and extent
of drug exposure because the neurotoxic effects differ with the type of
drug. Based on the observation that HIV infection is associated with cognitive
impairment/HIV dementia, the role of butyrylcholinesterase (BChE) in Alzheimer's
disease and metabolism of cocaine, Royal and his colleagues (see abstract
below) successfully examined sections of fixed brain from patients with
HIV-related cognitive impairment and from non-infected control subjects,
including individuals with Alzheimer's disease, for expression of this
enzyme. Their studies further highlight the utility of combining materials
for analysis from multiple sources and, therefore, the importance of even
more uniform approaches to the procurement, preparation, storage, and
distribution of banked materials.
Participants also pointed out that polydrug abuse, that occurs in the
real world, should be recognized and investigated as such. Blood samples
from each investigated case should be deposited, for example, in the central
NIDA-supported repository for genotyping. It is critical to use standardized
methods for compiling antemortem clinical data, disease and drug taking
histories and toxicology reports; and that clinical data are essential
not only for clinicopahological correlation but also for determining subtly
different subgroups within patient cohorts. Further, for example, lateral
asymmetry between brain hemispheres is important to understand the neuropathological
phenotype of drug abuse. Other issues such as gender differences in drug
susceptibility and the benefit of newer neuroimaging techniques (MRI,
fMRI and PET) were also discussed.
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