Elsevier

Behavioural Brain Research

Volume 365, 3 June 2019, Pages 198-209
Behavioural Brain Research

Research report
Sex and estrous cycle dependent changes in locomotor activity, anxiety and memory performance in aged mice after exposure of light at night

https://doi.org/10.1016/j.bbr.2019.03.015Get rights and content

Highlights

  • Locomotor, anxiety, novel object recognition of aged mice were studied.

  • Nocturnal behaviour of mice varied with sex and estrous cycle.

  • Light decreased locomotion and increased anxiety in proestrous females.

  • Light caused hyperactivity and reduction in anxiety in males and diestrous females.

  • Light caused failure of retention of object discrimination memory in all animals.

Abstract

Light-at-night (LAN) can affect mammalian behaviour. But, the effects of LAN on aged rodents remain undefined yet. In the present investigation, aged Swiss Albino mice, habituated in regular light-dark cycle, were exposed to bright-light-pulse (1-h) at night on the day of study followed by experimentations for assessment of locomotor activities in the open field, anxiety in the elevated plus maze and short-term memory for novel object recognition (NOR) in the habituated field. Under without-bright-light exposure, (a) aged proestrous females showed greater locomotor activities and less anxiety than in aged diestrous females, (b) aged males showed locomotor activities and anxiety level similar to aged diestrous females and aged proestrous females respectively and (c) all animals failed to retain in object discrimination memory. LAN exposure exhibited the continual failure of such retention of memory while animals showed free and spontaneous exploration with thigmotactic behaviour having no object bias and/or phobia, but time stay in objects by animals altered variably among sexes and stages of estrous cycle. Overall, the LAN caused (a) diminution in locomotor activities, rise in anxiety and failure of memory for recognition of both familiar and novel objects in aged proestrous females, (b) hyperlocomotor activities and reduction in anxiety in both males and diestrous females with the failure of memory for recognition of novel objects only in aged males while diestrous females showed enhanced exploration time to both objects during NOR. Thus, nocturnal behaviour of aged mice varies with sex and estrous cycle and light acts differentially on them.

Introduction

Light-at-night (LAN) causes deleterious effects on health and behaviour of humans and nocturnal animals including rodents [[1], [2], [3], [4], [5], [6]]. Nocturnal light stimuli are initially received by the retinal melanopsin-containing ganglion cells and then transmitted to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus via the retino-hypothalamic tract which finally disrupts melatonin release [[7], [8], [9], [10]]. Ageing in human is accompanied by the impaired visual system, gradual losses of neurons in SCN and other associated sub-cortical regions (raphe nuclei, reticular formation, pons, medulla, basal forebrain), reduction in melatonin and sensitivities of their receptors [8,11]. The phase advancement or phase delay of circadian rhythm is reported in elderly people [12]. Therefore, the adjustment of elderly people to light during night appears to be a serious challenge in modern society.

Epidemiological studies indicate that LAN brings about sleep deprivation [13] and depression [14] in elderly people. LAN is independently associated with obesity, impairment of lipid levels and an increase in night-time blood pressure without alterations of urinary melatonin excretion and glucose levels in elderly individuals studied under uncontrolled home setting [13,14]. LAN also adversely affects cognitive performances, particularly working memory and concentration without any alteration of a sustained attention task in elderly persons working in night shift [15,16]. LAN or changes in a circadian shift may increase the risk of breast and colorectal cancers in middle-aged (33–55 years) females [[17], [18], [19]]. Studies with different species of mice including transgenic mice (4–8 weeks old) indicate that constant light exposure accelerates ageing, disrupts metabolic processes, increases the risk of tumorigenesis and results in disturbances of the female reproductive cycle [[20], [21], [22], [23]].

Ageing is associated with structural and physiological changes in the brain that can account for age-related sensory and motor loss and gradual cognitive decline in rodents. Several behavioural studies with rodents of different ages (12, 18 and 25 months old) groups indicate that ageing is related to the reduction in locomotor activities (both vertical and horizontal) and an increase in anxiety-like behaviour in both sexes [[24], [25], [26], [27], [28]]. One study with SAMP8 mouse (10 months old) model indicates that the age-related anxiety levels are sex and behavioural task-specific [29]. The maximum amount of neuronal and non-neuronal cell losses has been found in neocortical regions (including hippocampus) during healthy ageing which in turn hampers the long-term spatial memory without affecting the long-term object recognition memory [[30], [31], [32]]. However, aged mice (9 months old) or rats (24 months old) habituated for short period (1 or 2 days) can perform the short-term object recognition memory [33,34]. Aged (24 months old) rats with cognitive impairments (measured in Morris water maze) show a reduction of motor activities without any alteration of anxiety in open field (OF) test and elevated plus maze (EPM) test compared to aged cognitively unimpaired or young rats where habituation to stimuli imparts an important role for behavioural output [35].

The effect of LAN has been extensively studied in young adult rodents too. Night-time light illumination (bright or dim) significantly reduces both general motor and rearing activities, increases anxiety-like behaviour in young adult (60–80 days old) rodents of both sexes during OF test and EPM test [[36], [37], [38]]. Our recent investigation with young (3 months old) Swiss Albino mice reveals that a single exposure of 1-h light-pulse at night alters behaviour of mice with respect to their sex variation and estrous cycle of females. This study indicates that LAN reduces locomotor activities, increases anxiety-like behaviour and fails to induce short-term memory (STM) task in young proestrous females while the locomotor activities and anxiety-like behaviour of males and diestrous females remain unaltered with decreases in STM performances [39]. However, the effects of LAN on aged mice remain undefined. The present study explores the changes in nocturnal locomotor activities, anxiety-like behaviour and short-term memory performances of aged male, proestrous and diestrous female mice using a single exposure (1-h) to bright light at early stages of the night as the putative factor for invoking such physiological changes.

Section snippets

Animal handling and habituation

Swiss Albino mice (8 males and 16 females; 20–22 months of age) were purchased from an authorized and registered vendor [Saha Enterprise, Kolkata, India; Committee for the purpose of control and supervision on experiments on animals (CPCSEA) registration number: 1828/PD/Bt/S/15/CPCSEA, Govt. registration number: 19BAEPS7949M1Z0] where animals were bred and kept in controlled laboratory conditions with regular light-dark cycle (12:12 h), temperature (22 ± 2 °C) and humidity (60%). Mice were

Results

In the present study, the normality test (Shapiro-Wilk test) designates that all the behavioural data sets of three experimental groups (aged males, proestrous females and diestrous females) were normally distributed (data not shown). The Bartlett test was performed to verify the assumption that variances were equal across aged males, diestrous females and proestrous females groups. The test statistics was larger than the critical value for each combination of data set and therefore the null

Discussion

The present study reports for the first time the effects of a single exposure of bright-LAN with 1-h duration on the nocturnal behaviour involving locomotion, anxiety and deficit in short-term memory performance of aged Swiss Albino mice with variations among sexes and stages of female reproductive cycle (proestrous and diestrous phases). The nocturnal behaviour of aged mice was evaluated under three different experimental fields having novel environments like circular big arena (surrounded by

Conflict of interest

The authors declare that there is no conflict of interest.

Acknowledgments

The present study was funded by the grant [BI 92(7)] of the University of Calcutta. We are thankful to Dr. Richard Mills (Vice President, Stoelting Co, USA), Dr. Anita Talawar (Managing Director, Gentech Marketing & Distribution (P) Ltd, India) and Mr. Sandip Majumder (Regional Sales Manager, Gentech Marketing & Distribution (P) Ltd, India) for their kind support to provide us the automated animal tracking software, ANY-Maze for collecting the experimental data.

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