Cancer and cancer survival modulates brain and behavior in a time-of-day-dependent manner in mice

Abstract

Improvements in breast cancer therapy/diagnosis have substantially increased the cancer survivor population, although many survivors report persistent mental health issues including fatigue, mood and anxiety disorders, and cognitive impairments. These behavioral symptoms impair quality-of-life and are often associated with increased inflammation. Nocturnal rodent models of cancer are critical to the identification of the neurobiological mechanisms underlying these behavioral changes. Although both behavior and immunity display distinct diurnal patterns, most rodent research in this field is performed during the rodents’ inactive (light) period, which could potentially undermine the conclusions and clinical relevance. Therefore, here we tested the extent to which mammary tumors or tumor resection (“survivors”) in mice affects behavior and neuroinflammation in a nyctohemeral (day versus night)-dependent manner. Indeed, only the dark (active) phase unmasked fatigue-like behavior and altered novel object investigation for both tumor-bearing and -resected mice relative to surgical controls. Several inflammatory markers were expressed in a time-of-day-dependent manner (lower in the dark phase) in the blood and brains of surgical control mice, whereas this temporal pattern was absent (IL-1β, CXCL1, Myd88 , Cd4 ) or reversed ( C3 ) in the respective tissues of tumor-bearing and -resected mice. Taken together, these data indicate that the time of day of assessment significantly modulates various persistent and transient tumor-induced behavioral and immune changes.

Targeted systemic dendrimer delivery of CSF‐1R inhibitor to tumor‐associated macrophages improves outcomes in orthotopic glioblastoma

“…Rearing behavior an exploratory instinct used in behavioral neuroscience as a marker for fear/anxiety associated with disease burden 47 . Mobility in open field experiments as a proxy for anxiety and fatigue has been shown to correlate with tumor burden, with mice exhibiting decreased mobility when inoculated with tumors and partial recovery upon tumor resection 48,49 . Here we demonstrate that in addition to prolonging survival and reprogramming the tumor immune environment, a single systemically administered dose of DBLZ can significantly improve QoL measures in this model through specific BLZ delivery to brain tumor TAMs and systemic clearance intact via kidneys over ~48 h. Such measurements of patient wellbeing apart from overall survival are underexplored in preclinical anticancer studies and may provide a more wholistic evaluation of therapeutic efficacy.…”

“…A score between 0 and 3 was assigned, with 0 indicating healthy posture and 3 indicating severe curvature that does not resolve upon movement. To assess motor function as a marker of cancer progression, 48 mice were recorded in open field experiments on days 12, 15, and 18 postinoculation. Mice were recorded for 10 min in an isolated environment and analyzed for distance traveled and velocity with EthoVision XT video tracking software (Noldus Information Tech, Inc., Leesburg, Virginia).…”

Cytokines profile in neonatal and adult wild-type mice post-injection of U. S. pediatric vaccination schedule

“…The experimenter was blinded to the identity of the plasma samples. This MSD kit and method has been used and validated by a number of scientific studies ( Soh et al., 2016 ; Wiehagen et al., 2017 ; Xu et al., 2018 ; Burmeister et al., 2019 ; Santos et al., 2019 ; Song et al., 2019 ; Pang et al., 2020 ; Unger et al., 2020 ).…”

Pathophysiological Aspects of Inflammation and Drug Design: an Updated Overview

“…16 No SNC, a progressão da inflamação acarreta em maior quantidade de células neuronais danificadas, alterando substancialmente as funções cognitivas e motoras, afetando diferentes áreas do cérebro e diferentes tipos de neurônios, o que explica o processo neuroinflamatório reconhecidamente como uma das características mais marcantes e comuns nas doenças neurodegenerativas (DNs), a exemplo da doenças de Parkinson (DP), Alzheimer (DA) e Huntington (DH) e das escleroses múltipla (EM) e Esclerose Lateral Amiotrófica (ELA). 15,17 Além disso, muitas outras doenças crônicas são atualmente compreendidas por seu marcante componente inflamatório, como a diabetes tipo 2, Figura 2. Características do processo inflamatório agudo (A) e crônico (B) 2,11 Figura 3.…”

“…34,40 Nesta mesma época, foram descobertos os derivados de ácidos antranílicos, ou fenematos, com propriedades anti-inflamatórias e analgésicas, levando ao desenvolvimento de fármacos indicados para o tratamento de artrite, dores musculares e dismenorreia, representados pelo ácido meclofenâmico (7), ácido flufenâmico (8), ácido tolfenâmico (9) e ácido mefenâmico (10,Figura 10), que atuam como inibidores não-seletivos de COX-1 e COX-2. (17,Figura 10), ganhando destaque na terapêutica. 36,40,54,58,59 Uma outra classe de AINEs seletivos para COX-1, com destaque por sua importância terapêutica, foi da família dos oxicans (18), exemplificada pelo piroxicam (19).…”