Z01MH02253       FREED, W J                BRAIN TISSUE TRANSPLANTATION
-PROJECT NUMBER......1 Z01 MH02253-10
                                     FY  94    FREED, W J
IRG/INTRAMURAL UNIT..NPB                       NIMH, NIH
AWARD AMOUNT.........         $0

PERFORMING ORGANIZATION:
TITLE   BRAIN TISSUE TRANSPLANTATION

ABSTRACT:

This project involves studies of plasticity and functional consequences
of changes in the striatal afferent systems, especially the
dopaminergic afferents derived from the substantia nigra and the
glutamatergic afferents derived from the cerebral cortex. Techniques
employed involve: (i) transplanting tissues containing catecholamines
or L-DOPA (i.e., adrenal medulla, tumor cells, genetically altered
cells, and embryonic brain tissue) into the brain, (ii) biochemical and
pharmacological studies, and (iii) studies using tissue culture models.
The purpose of these experiments is in part to: (A) elucidate the
properties of these tissues after transplantation and the response of
the host brain to the transplanted tissues, and (B) to investigate
mechanisms of neuronal adaptation and plasticity in response to injury
and chronic pharmacological treatments. Specifically, (A) these
experiments employ animal models to: (1) develop the techniques of
brain tissue transplantation for clinical use in Parkinson's disease;
(2) develop brain tissue transplantation techniques which eventually
may be applicable to other disorders such as schizophrenia and
epilepsy, if and when these disorders become sufficiently understood
to permit such applications; (3) develop alternate cell types, such as
immortalized neurons, for transplantation into the brain and
corresponding in vitro model studies of cellular differentiation and
cell-cell interactions; and (4) elucidate the factors controlling brain
development and brain response to injury or impairment, with particular
emphasis on the nigrostriatal dopamine system.  (B) The second purpose
of these experiments is primarily aimed at elucidating the interactions
between functions of: (a) the glutamate-mediated corticostriatal system
and related anatomical systems, and (b) dopaminergic systems, including
the nigrostriatal system; and the functional effects of stimulant and
neuroleptic drugs.  The ultimate purpose of these studies is to enhance
our understanding of the mode of action of neuroleptics and possibly
brain dysfunction in schizophrenia.  Secondary purposes are to enhance
our understanding of the mechanisms of stimulant drug effects and
alcohol addiction; to develop compounds with potential utility for the
acute treatment of stimulant overdose, schizophrenia, and seizure
disorders; and to understand the possible forms of plasticity in the
corticostriatal system.  During the past reporting year, significant
progress has been made in these areas.

CRISP INDEXING TERMS FROM CRISP THESAURUS:
04893273P   brain injury
20519653P   nervous system regeneration
20520588P   nervous system transplantation
20573689P   Parkinson's disease
20592257P   neural plasticity
04795797S   substantia nigra
04804134S   cerebral cortex
04856986S   epilepsy
05924376S   cell cell interaction
06001092S   cell differentiation
07777405S   dihydroxyphenylalanine
08811632S   glutamate
19449483S   disease model
20434430S   afferent nerve
20535572S   neuroanatomy
20536900S   developmental neurobiology
20591618S   neuropharmacology
22685010S   catecholamine
22685256S   dopamine
24850932S   schizophrenia
40000369S   immortalized cell
10167191T   embryo /fetus cell /tissue
29355444T   tissue /cell culture