Molecular and Chemical Neuropathology

, Volume 30, Issue 3, pp 239–252 | Cite as

Retinoic acid synthesis in normal and alzheimer diseased brain and human neural cells

  • Michael J. Connor
  • Neil Sidell
Original Articles

Abstract

Retinoids play fundamental roles in CNS development, but their distribution, metabolism, and function within the mature human CNS are unknown. In these studies, extracts of autopsy tissues recovered from histopathologically confirmed control and Alzheimer diseased brains were tested for their ability to synthesize retinoic acid. Retinaldehyde dehydrogenase (RLDH), the enzyme that forms retinoic acid from retinaldehyde, was present in hippocampus, frontal cortex, and parietal cortex. The RLDH activity of hippocampus and partietal cortex from Alzheimer diseased brains was 1.5- to 2-fold higher (p<0.05) compared to the controls. In contrast, the RLDH activity of frontal cortex was the same for both Alzheimer diseased and control groups. A cultured human glioblastoma (U251) and neuroblastoma (LA-N-5) cell line synthesized retinoic acid from retinaldehyde or retinol, suggesting that a variety of neural cell types possess this activity. LA-N-5 cells grown in vitamin A-depleted medium had higher (p<0.05) RLDH activity (0.35±0.04 nmol/mg/h) than LA-N-5 cells grown in vitamin A-replete media (0.15±0.02 nmol/mg/h). This difference was lost when retinol was added back to the medium, confirming that a reduction in vitamin A supply can induce RLDH activity in neural cells. However, this feedback mechanism does not appear to explain the higher RLDH activity of Alzheimer diseased hippocampus and parietal cortex, because the overall vitamin A status as indicated by serum retinol and carotenoid levels and by hippocampal retinoid content was similar for the Alzheimer diseased and control groups. These studies establish the presence of retinoids and RLDH activity in human brain tissues, and indicate that retinoic acid synthesis is modulated in some regions of Alzheimer diseased brain.

Index Entries

Alzheimer disease retinoic acid vitamin A retinaldehyde dehydrogenase neuroblastoma (LA-N-5) cells hippocampus parietal cortex frontal cortex 

Abbreviations

FCS

fetal calf serum

RLDH

retinaldehyde dehydrogenase

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Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  • Michael J. Connor
    • 1
  • Neil Sidell
    • 2
  1. 1.Division of Dermatology, Department of MedicineUCLA School of MedicineLos Angeles
  2. 2.Department of Pathology and Laboratory MedicineUCLA School of MedicineLos Angeles

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