Section: Research

Peter McCaffery, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Cell Biology

Other Affiliation(s):
   Program in Neuroscience
   Shriver Center

Dr. McCaffery relocated to the University of Aberdeen, Scotland in March, 2006

Vitamin A, Retinoic Acid and Control of Brain Development and Function

Drugs such as tretinoin, isotretinoin and Accutane® are used to treat a diverse range of clinical disorders -- skin diseases such as psoriasis and acne, cancers including leukemia and prostate cancer, and AIDS. The chemical name for these drugs is retinoic acid (RA), the acid form of vitamin A.   RA is a natural compound, normally synthesized in the developing embryo, regulating tissues which are actively dividing. When human embryos are exposed to RA in excess, however, their development is severely disrupted thus RA used as a drug is highly teratogenic. Dr. McCaffery studies the enzymes that control the normal production of RA in the brain. He is examining the effects of injected RA on the developing brain of the mouse and concentrating on the cerebellum, the region of the brain central to the coordination of movement. Low levels of RA are normally produced in the brain to regulate development; excess of RA following Accutane® treatment disrupts cerebellar organization. The effects of RA on the cerebellum resemble that of several genetic disorders, suggesting the possibility that some genetic diseases may result from a hereditary disturbance in normal retinoic acid levels.

Accutane® may also influence the adult brain.  The effects of RA on the adult may have parallels to its effects in the embryo in that RA influences the "embryonic-like" regions of the adult brain i.e. those areas in which birth of new neurons continues throughout life.  We have shown in the mouse that neurogenesis in these areas, the hippocampus and the subventricular zone, is suppressed by RA.   A severe behavioral phenotype also results in which the mice are deficient in their ability to learn a maze task, implying that RA may influence human behavior.

Ongoing Projects

Retinoic Acid and Migrating Neurons in the Developing Hindbrain

Retinoic Acid and Hippocampal Neurogenesis

Phone: (781) 642-0172
E-mail: Peter.McCaffery.Forward@umassmed.edu
Keywords: Neurobiology

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