# METABOLIC & DEVELOPMENTAL ASPECTS OF MENTAL RETARDATION

> **NIH NIH P01** · UNIVERSITY OF MARYLAND BALTIMORE · 1994 · $584,097

## Abstract

The major thrust of this amended application continues to be a
multidisciplinary approach to study the mechanisms that regulate metabolic
activities and differentiating events in the developing central nervous
system. During the past five years the research supported by this Program
Project Grant has been instrumental in establishing that various neural
cell types have markedly different specificities with regard to the
substrates they utilize. Since alterations in the patterns of substrate use
during development may cause abnormal neural function manifested as mental
retardation, the proposed studies focus upon the biochemical development of
specific types of neural cells, individually and in interaction with each
other, as well as the regulatory mechanisms that control their utilization
of substrates. Furthermore the blood brain barrier changes adramatically
during early development and changes in this process could also result in
major neurological damage. To understand these interrelationships requires
a comprehensive delineation of regulatory mechanisms underlying neural
development. Such mechanisms include the regulation of gene expression,
substrate transport, as well as regulatory mechanisms involving
precursor-product relationships, post-translational modifications of key
proteins, intracellular translocation, and intercellular trafficking of
metabolites. The four projects address one or more aspects of this research
theme both as individual investigations and as collaborative efforts. The
role of carrier mediated transport, changes in pool sizes of metabolites,
and effects on specific enzyme activities in the regulation of the
metabolic fates of ketone bodies, malate and lactate will be the emphasis
of one project. A second project will determine the molecular mechanism
underlying the expression of glutamine synthetase and glutaminase
activities in specific brain cells and how the regulation of these enzymes
affects compartmentation, metabolic trafficking and oxidative metabolism. A
third project uses a novel monoclonal antibody as a probe to characterize
the developing blood brain barrier. The fourth project will focus on the
modulatory properties of the S1OO Beta protein in specific brain cells and
on effectors which regulate choline acetyl transferase activity. The
results from this integrated, multidisciplinary approach should enhance our
understanding of the complex metabolic alterations underlying many types of
mental retardation and they will also provide guidance for the clinical
management of infants with developmental disabilities.

## Key facts

- **NIH application ID:** 2197327
- **Project number:** 5P01HD016596-11
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** J T TILDON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $584,097
- **Award type:** 5
- **Project period:** 1982-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197327

## Citation

> US National Institutes of Health, RePORTER application 2197327, METABOLIC & DEVELOPMENTAL ASPECTS OF MENTAL RETARDATION (5P01HD016596-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197327. Licensed CC0.

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