HARVARD MEDICAL SCHOOL

LABORATORY OF Warren Anatomical Museum
Harvard Medical School

Boston 15, Massachusetts

CELLULAR NEUROPATHOLOGY

 

Dr. Joshua Lederberg

Department of Genetics

Stanford University Medical Center
Palo Alto, California

Dear Dr. Lederberg:

I am enclosing reprints of our papers on autoradiographic
studies of neural development, as you requested.

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You asked about evidence on DNA turnover in the absence
of mitosis in neurons. No data are available. Causey and
Stratmann (J. Anat. 1959 93:341-347) studied neurons of the
rabbit superior cervical ganglion at time intervals after
denervation, up to 28 days. They measured relative DNA con-
tent in neuron nuclei by Feulgen microspectrophotometry and
recorded a progressive fall from 85 units to about 50 units
in about two weeks time after nerve section. They suggested
that neuronal DNA may be labile, at least in part, and suggest-
ed a few possible reasons why. They did not extend the
measurements long enough to learn if the 2n value would have
been restored. If their data are correct, a neuron either
retains permanent evidence of injury (lowered DNA content)
or resynthesizes DNA in the absence of cell division.

7171199

Our own published observations extend only to 30 days
beyond birth and we did not recognize loss of tritium during
that time. However, em I am sure you recognize that such a
statement is not worth much unless one makes accurate and
representative grain counts, measures nuclear sizes (which
change postnatally) and corrects for variations in histological
methods, autoradiographic emulsion, development time, etc.

I hope to have a reasonable answer to your question in
about two to three months. We have a series of animals
page 2

injected with thymidine-H3 at various embryonic stages and
killed at two years of age. These are being processed now.
We also have littermates in the same series, but killed at
earlier postnatal ages.

The neuroglia present another problem. The best data
are those of Smart and Leblond (J. Comp. Neur. 1961 116:
349-367). Their tables, especially Table 2, suggest either
DNA turnover or mitosis. Little evidence of mitosis was
found, even with the aid of colchicine. There are several
possible explanations for these data, including DNA turn-
over. You might also glance at another of Leblond's papers
in Am. J. Anat. 1960 106:247-285, especially page 257.

Assuming DNA half-life of neurons is very long, it is
possible that these specialized cells may depend on neuro-
glial cells to do things for them in a symbiotic senge,
things which other cells do for themselves and which in-
volve DNA turnover. However, even these crude speculations
are best deferred for a few months until we have some de-
cent numbers.

Thank you very much for your interest. I will write
again when I have something to say. Please give my warmest
regards to Cliff Grobstein.

Sincerely,
w g ‘ Ge on ee ALL
Richard L. Sidman, M.D.

Laboratory of Cellular Neuropathology

Harvard Medical School
Boston 15, Massachusetts

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