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Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice
induces behavioural and biological changes relevant to depression
#MMPMID28440814
Egeland M
; Guinaudie C
; Du Preez A
; Musaelyan K
; Zunszain PA
; Fernandes C
; Pariante CM
; Thuret S
Transl Psychiatry
2017[Apr]; 7
(4
): e1101
PMID28440814
show ga
Numerous studies have examined links between postnatal neurogenesis and
depression using a range of experimental methods to deplete neurogenesis. The
antimitotic drug temozolomide (TMZ) has previously been used successfully as an
experimental tool in animals to deplete adult neurogenesis and is used regularly
on human patients as a standard chemotherapy for brain cancer. In this study, we
wanted to evaluate whether TMZ as a model for chemotherapy treatment could affect
parameters related to depression in an animal model. Prevalence rates of
depression in patients is thought to be highly underdiagnosed, with some studies
reporting rates as high as 90%. Results from this study in mice, treated with a
regimen of TMZ similar to humans, exhibited behavioural and biochemical changes
that have relevance to the development of depression. In particular, behavioural
results demonstrated robust deficits in processing novelty and a significant
increase in the corticosterone response. Quantification of neurogenesis using a
novel sectioning method, which clearly evaluates dorsal and ventral neurogenesis
separately, showed a significant correlation between the level of ventral
neurogenesis and the corticosterone response. Depression is a complex disorder
with discoveries regarding its neurobiology and how it relates to behaviour being
only in their infancy. The findings presented in this study demonstrate that
chemotherapy-induced decreases in neurogenesis results in previously unreported
behavioural and biochemical consequences. These results, we argue, are indicative
of a biological mechanism, which may contribute to the development of depression
in patients being treated with chemotherapy and is separate from the mental
distress resulting from a cancer diagnosis.
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