"No hippocampal neuronal death following chronic HU210 treatment"
We examine the total number of the dentate granule and
CA3 pyramidal neurons following twice-daily injections of HU210
(100 μg/kg) for 10 days. As depicted in Figure 7A, HU210-treated
rats did not show detectable loss of NeuN-immunopositive neurons
in the hippocampus, relative to naive control rats. Stereological
cell counting confirmed that no significant difference in the
total number of the dentate granule cells and CA3 pyramidal neurons between naive and HU210-treated rats. These results, however, do not
exclude the possibility that some of NeuN-stain neurons following
chronic HU210 treatment shown in Figure 7A are dying. Accordingly,
we used TUNEL stain and Fluoro-Jade B stain to examine the
degenerating hippocampal neurons (Zhang, X., et al. 2002. Relations between brain pathology and temporal lobe epilepsy. J. Neurosci.) in rats receiving chronic HU210 treatment, with the naive rats as negative control and kainic acid treated rats as positive control (Zhang, X, et al, 2002)). We failed to detect any TUNEL- or Fluoro-Jade B stained degenerating cells throughout the whole hippocampus in both naive rats and HU210-treated rats, whereas kainic acid injected rats showing epileptic status exhibited numerous dying cells in the CA3 pyramidal cell layer and
even dentate granule cell layer .
We employed the same behavioral tests to examine the effects of chronic HU210 treatment on measures of anxiety and depression.
Cell counting revealed an overall significant difference in the number of BrdU-stained cells in the dentate gyrus
HU210-treated rats displayed a significant increase (P < 0.05)
in the number of BrdU-positive cells in the dentate gyrus, whereas
AM281-treated rats exhibited no significant difference (P = 0.165).
These data together suggest that chronic HU210 treatment
promoted hippocampal neurogenesis and exerted anxiolytic- and
antidepressant-like effects.
To determine the relationship between hippocampal neurogenesis and anxiolytic- and antidepressant-like effects produced by chronic HU210, we examined the effects of a selective destruction of the hippocampal neural
stem cells on the behavioral effects of chronic HU210.
...our results together suggest
that chronic HU210 treatment reduced anxiety and depression,
likely via promoting hippocampal neurogenesis.
http://www.jci.org/cgi/reprint/115/11/3104.pdf
These data together suggest that chronic HU210 treatment
promoted hippocampal neurogenesis and exerted anxiolytic- and
antidepressant-like effects.
To determine the relationship between hippocampal neurogenesis and anxiolytic- and antidepressant-like effects produced by chronic HU210, we examined the effects of a selective destruction of the hippocampal neural
stem cells on the behavioral effects of chronic HU210.
...our results together suggest
that chronic HU210 treatment reduced anxiety and depression,
likely via promoting hippocampal neurogenesis.
http://www.jci.org/cgi/reprint/115/11/3104.pdf