Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer

Rendeiro, Catarina; Sheriff, Andrew; Bhattacharya, Tushar K.; Gogola, Joseph V.; Baxter, Jeffrey H.; Chen, Hong; Helferich, William G.; Roy, Edward J.; Rhodes, Justin S.

doi:10.1016/j.bbr.2016.07.043

Cited by 43 publications

(29 citation statements)

References 95 publications

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“…Although it is not possible to experimentally deplete adult neurogenesis in humans, this study gives strong evidence that chemotherapy-induced decreases in adult neurogenesis may affect the stress response and behaviours related to processing novelty, both of which ultimately may contribute to depressive symptoms. In addition to TMZ, the antimitotic action of other cancer drugs has already been demonstrated in animal models to decrease neurogenesis and affect spatial memory, 42 though these do not affect neurogenesis-independent functions such as fear conditioning and novel object recognition. 43 Although no changes in depressive-like behaviour have been noted in other studies, it is likely that other types of chemotherapy may similarly affect behaviours and biological parameters, which have the potential to contribute to depression.…”

Section: Discussionmentioning

confidence: 99%

Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression

et al. 2017

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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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Section: Discussionmentioning

confidence: 99%

Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression

et al. 2017

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“…Test. All mice received the Morris water maze (MWM) test after the establishment of infrasound-induced CNS injury model [33]. An escaping platform was placed in the quadrant IV of a pool at one cm under water surface on from 1 to 4 d and removed on 5 d. If a mouse could not find the platform within one min, it would be placed on the platform for 15 s. The mice were trained for 4 d to find the plate.…”

Section: Spatial Learning and Memorymentioning

confidence: 99%

Tetrahydroxystilbene Glucoside Ameliorates Infrasound-Induced Central Nervous System (CNS) Injury by Improving Antioxidant and Anti-Inflammatory Capacity

Zhou

Yang

Fan

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Infrasound is a major threat to global health by causing injuries of the central nervous system (CNS). However, there remains no effective therapeutic agent for preventing infrasound-caused CNS injury. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glycoside (THSG) exerts protective function against CNS injuries and may have beneficial effects on infrasound-induced CNS impairment. Methods. A mouse model with CNS (oxidative stress-induced inflammation and neuronal apoptosis) injuries was established when the mouse was exposed to the infrasound of 16 Hz at 130 dB for 2 h each day and the duration of treatment was 8 d. The mice were divided into the control (CG, healthy mice), the model (MG, model mice), and the THSG (EG, experimental group, model mice treated with THSG) groups. The learning and memory impairments caused by infrasound were examined using a Morris water maze test. Lipid profiles, antioxidant biomarkers, and inflammatory cytokines in hippocampus tissue were measured by using corresponding ELISA kits. Meanwhile, BCL-2/BAX/caspase-3 signaling pathway was measured in the hippocampi and prefrontal cortex of the mouse brain using real-time qPCR and Western blot. Nissl’s stain was used to measure neuronal necrosis in the hippocampi and prefrontal cortex of the mouse brain. Results. THSG significantly ameliorated the learning and memory impairments caused by infrasound. On the other hand, THSG improved lipid profiles, increased antioxidant properties by affecting the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA), and displayed anti-inflammatory action via the downregulation of IL- (interleukin-) 6, IL-8, IL-10, TNF- (tumor necrosis factor-) α, and hs-CRP (high-sensitivity C-reactive protein) in the hippocampal tissues of the mouse model (P<0.05). Additionally, Nissl’s stain showed that THSG inhibited infrasound-induced neuronal necrosis in the hippocampi and prefrontal cortex. Besides, THSG exerted antiapoptosis function by upregulating the level of Bcl-2 and downregulating the levels of BAX and caspase-3 in the hippocampi. Conclusion. THSG may be an effective anti-infrasound drug against CNS injury by improving antioxidant, anti-inflammatory, antiapoptosis, and antinecrosis capacities. Further research is still needed to confirm the exact molecular mechanism.

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“…There is also experimental evidence that documents the deterioration of cognitive functioning after chemotherapy. Rendeiro et al observed cognitive impairments, similar to those in patients, in C57BL/6J mice treated with cyclophosphamide, doxorubicin and 5-fluorouracil (12).…”

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confidence: 66%

The Mystery of Chemotherapy Brain: Kynurenines, Tubulin and Biophoton Release

Sordillo

2020

Anticancer Res

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The majority of patients receiving chemotherapy experience post-chemotherapy cognitive impairment, sometimes referred to as "chemo brain" or "chemo fog." The cognitive impairment associated with this syndrome can be severe, and can sometimes last for many years after therapy discontinuation. Despite extensive investigations, its etiology is unknown. We argue that chemo brain results from damage to tubulin within microtubules. This damage can occur directly from tubulin inhibitors such as taxanes, epothilones or vinca alkaloids. Other chemotherapies stimulate increased mitochondrial activity and biophoton release. This results in abnormal tryptophan metabolism and excess production of neurotoxic kynurenines, which, in turn, damage microtubules.

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Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer

Cited by 43 publications

References 95 publications

Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression

Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression

Tetrahydroxystilbene Glucoside Ameliorates Infrasound-Induced Central Nervous System (CNS) Injury by Improving Antioxidant and Anti-Inflammatory Capacity

The Mystery of Chemotherapy Brain: Kynurenines, Tubulin and Biophoton Release

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