Increasing dietary choline attenuates spatial memory deficits resulting from exposure to the chemotherapeutic agents cyclophosphamide and doxorubicin

Abstract

Background: Choline supplementation (+Ch) improves cognitive function in impaired animals and humans. Chemotherapy-related cognitive deficits (CRCDs) occur in cancer patients, and these deficits persist following treatment, adversely impacting quality of life. To date, there are no approved treatments for this condition. Aim: Because +Ch improves impaired memory, it was of interest to determine whether +Ch can attenuate spatial memory deficits induced by the chemotherapeutic agents doxorubicin (DOX) and cyclophosphamide (CYP). Methods: Female BALB/C mice, 64 days of age, were trained in the Morris water maze and baseline performance determined on day 15. Following baseline assessment, mice were placed on +Ch diet (2.0% Ch) or remained on standard diet (0.12% Ch). Mice received intravenous injections of DOX (2.5 mg/kg) and CYP (25 mg/kg), or equivalent volumes of saline (0.9% NaCl), on days 16, 23, 30, and 37, and spatial memory was assessed weekly from day 22 to 71. Results: DOX and CYP produced a prolonged impairment in spatial memory as indicated by an increased latency to the correct zone ( p < 0.05), and a decrease in time in the correct zone ( p < 0.05), % of total swim distance in the correct zone ( p < 0.05) and % entries to the correct zone ( p < 0.05). These effects were attenuated by +Ch. Conclusion: Although it remains to be determined whether this effect extends to other cognitive domains and whether +Ch is prophylactic or therapeutic, these findings suggest that +Ch may be an effective intervention for CRCDs.

Letrozole delays acquisition of water maze task in female BALB/c mice: possible involvement of anxiety

“…The results of the reversal test proved that highly anxious mice can learn the water maze task, but they require a longer training to initiate searching in the center of the maze. Occurrence of highly anxious BALB/c mice that predominantly float has been reported by others (Francis et al, 1995;Johns et al, 2021;Philpot et al, 2016;Wahlsten et al, 2005). In some studies, such mice were excluded from testing.…”

“…In some studies, such mice were excluded from testing. One study (Philpot et al, 2016) described removal from the study of 13 of 38 females, and 1 of 18 males, and other (Johns et al, 2021) described removal of 16 of 50 females. In those studies, water was kept at 24 °C.…”

Choline alleviated perinatal fluoride exposure‐induced learning and memory impairment through α4β2 nAChRs and α7 nAChRs in offspring mice

“…Choline, a strong organic base and a constituent of lecithin, is widely added to human food and animal feed to ensure the health of humans and animals and improve the production performance of livestock and poultry. It is present in sphingomyelin and is a precursor of the neurotransmitter acetylcholine 22 . As a neurotransmitter, acetylcholine's increase can speed up the transmission of information and increase the brain's activity 23 .…”

“…Specifically, Moreno et al found that prenatal choline supplementation could accelerate the development of long‐term memory in offspring rats 27 . Moreover, Johns et al reported that choline supplementation alleviated chemotherapeutic‐induced spatial memory deficits 22 . Lots of studies have confirmed the toxic effects of fluoride on the offspring's nervous system and learning and memory ability 15,28 .…”

Translational psychopharmacology

“…Johns and colleagues' report findings that support the use of Choline supplementation (+Ch) as an intervention for chemotherapy-related cognitive deficits and suggest that impairments of hippocampal-mediated cognitive function following exposure to chemotherapeutic agents, doxorubicin and cyclophosphamide may be the result of altered cholinergic function (Johns et al, 2021). They recommend that further studies are necessary to determine if +Ch provides similar benefits in individuals with tumours, and importantly, whether +Ch contributes to tumour development and growth or adversely impacts the effectiveness of chemotherapy.…”