Feeding behavior modifies the circadian variation in RR and QT intervals by distinct mechanisms in mice.

Rhythmic feeding behavior is critical for regulating phase and amplitude in the ≈24-h variation of heart rate (RR intervals), ventricular repolarization (QT intervals), and core body temperature in mice. We hypothesized changes in cardiac electrophysiology associated with feeding behavior were secondary to changes in core body temperature. Telemetry was used to record electrocardiograms and core body temperature in mice during ad libitum-fed conditions and after inverting normal feeding behavior by restricting food access to the light cycle. Light cycle-restricted feeding modified the phase and amplitude of 24-h rhythms in RR and QT intervals, and core body temperature to realign with the new feeding time. Changes in core body temperature alone could not account for changes in phase and amplitude in the ≈24-h variation of the RR intervals. Heart rate variability analysis and inhibiting ß-adrenergic and muscarinic receptors suggested that changes in the phase and amplitude of 24-h rhythms in RR intervals were secondary to changes in autonomic signaling. In contrast, changes in QT intervals closely mirrored changes in core body temperature. Studies at thermoneutrality confirmed that the daily variation in QT interval, but not RR interval, primarily reflected daily changes in core body temperature (even in ad libitum-fed conditions). Correcting the QT interval for differences in core body temperature helped unmask QT interval prolongation after starting light cycle-restricted feeding and in a mouse model of long QT syndrome. We conclude feeding behavior alters autonomic signaling and core body temperature to regulate phase and amplitude in RR and QT intervals, respectively.NEW & NOTEWORTHY We used time-restricted feeding and thermoneutrality to demonstrate that different mechanisms regulate the 24-h rhythms in heart rate and ventricular repolarization. The daily rhythm in heart rate reflects changes in autonomic input, whereas daily rhythms in ventricular repolarization reflect changes in core body temperature. This novel finding has major implications for understanding 24-h rhythms in mouse cardiac electrophysiology, arrhythmia susceptibility in transgenic mouse models, and interpretability of cardiac electrophysiological data acquired in thermoneutrality.

New role for cardiomyocyte Bmal1 in the regulation of sex-specific heart transcriptomes.

It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the the core clock genes are expressed in common in both sexes but the circadian transcriptome of the mouse heart is very sex-specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts and the temporal pattern of REGs was distinctly different between sexes. We next used a cardiomyocyte-specific knock out of the core clock gene, Bmal1, to investigate its role in sex-specific gene expression in the heart. All sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss of Bmal1. Surprisingly, loss of cardiomyocyte Bmal1 also resulted in a roughly 8-fold reduction in the number of all the differentially expressed genes between male and female hearts. We conclude that cardiomyocyte-specific Bmal1, and potentially the core clock mechanism, is vital in conferring sex-specific gene expression in the adult mouse heart.

Circadian Regulation of Cardiac Arrhythmias and Electrophysiology.

Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns of triggers for sudden cardiac death, the incidence of sudden cardiac death, and cardiac arrhythmias. This review highlights historical and contemporary studies examining the role of day/night rhythms in the timing of cardiovascular events, delves into changes in the timing of these events over the last few decades, and discusses cardiovascular disease-specific differences in the timing of cardiovascular events. The current understanding of the environmental, behavioral, and circadian mechanisms that regulate cardiac electrophysiology is examined with a focus on the circadian regulation of cardiac ion channels and ion channel regulatory genes. Understanding the contribution of environmental, behavioral, and circadian rhythms on arrhythmia susceptibility and the incidence of sudden cardiac death will be essential in developing future chronotherapies.

Feeding Behavior Modifies Daily Rhythms in Autonomic Signaling and Core Body Temperature to Shape 24-hour Rhythms in Cardiac Electrophysiology.

Circadian rhythms in physiology and behavior are intrinsic ~24-hour cycles regulated by biological clocks (i.e., circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. Studies suggest that circadian clock signaling in the suprachiasmatic nucleus of the hypothalamus and cardiomyocytes shape day/night rhythms in cardiac electrophysiology (i.e., RR and QT intervals). However, studies also show that the day/night rhythm of the RR and QT intervals depends on the timing of feeding in mice. This study determined the mechanisms for how feeding impacts day/night rhythms in the RR and QT intervals in mice. Telemetry was used to record electrocardiograms, core body temperature, and activity in mice during ad libitum-fed conditions and after inverting normal feeding behavior by restricting the timing of feeding to the light cycle. Light-cycle restricted feeding caused a simultaneous realignment of RR, QT, and PR intervals and body temperature to the new feeding time. Correcting the QT interval for body temperature eliminated the 24-hour rhythm in the QT interval. Estimating the impact of temperature on RR intervals did not account for the daily change in the RR interval during light-cycle restricted feeding. Cross-correlation analysis suggested daily rhythm in RR intervals correlated with heart rate variability measures but not activity. Injecting mice undergoing light cycle-restricted feeding with propranolol and atropine caused a complete loss in the 24-hour rhythm in the RR interval. We conclude that feeding behavior impacts body temperature and autonomic regulation of the heart to generate 24-hour rhythms in RR and QT intervals.

Artificial night illumination disrupts sleep, and attenuates mood and learning in diurnal animals: evidence from behavior and gene expression studies in zebra finches.

This study investigated the effects of an illuminated night on sleep, mood, and cognitive performance in non-seasonal diurnal zebra finches that were exposed for 6 weeks to an ecologically relevant dimly lit night (12L:12dLAN; 150 lx: 5 lx) with controls on the dark night (12L:12D; 150 lx: < 0.01 lx). Food and water were provided ad libitum. Under dLAN (dim light at night), birds showed disrupted nocturnal (frequent awakenings) and overall decreased sleep duration. They also exhibited a compromised novel object exploration, a marker of the bird's mood state, and committed more errors, took significantly longer duration to learn with low retrieval performance of the learned task when tested for a color-discrimination (learning) task under the dLAN. Further, compared to controls, there was reduced mRNA expression level of genes involved in the neurogenesis, neural plasticity (bdnf, dcx and egr1) and motivation (th, drd2, taar1 and htr2c; dopamine synthesis and signaling genes) in the brain (hippocampus (HP), nidopallium caudolaterale (NCL), and midbrain) of birds under dLAN. These results show concurrent negative behavioral and molecular neural effects of the dimly illuminated nights, and provide insights into the possible impact on sleep and mental health in diurnal species inhabiting an increasingly urbanized ecosystem.

Differential effects of continuous and intermittent daytime food deprivation periods on metabolism and reproductive performance in diurnal zebra finches.

We investigated whether food availability effects on metabolism and reproduction are the result of the sum effect of daily feeding (food availability) and starvation (food deprivation) periods. Adult zebra finches were paired and subjected to a time-restricted feeding (TRF) regimen consisting of continuous and intermittent daytime food deprivation periods. Birds were given food during the 12-h day for a total of 4-h in the evening (1 *4-h, hour 8-12), or in 2 splits of 2 h each (2 * 2-h) or 4 splits 1 h each (4 * 1-h), with controls on food ad libitum, until they had the first egg clutch. TRF caused significant changes in hepatic expression of metabolism-associated sirt1, egr1, pparα and foxo1 genes despite no difference in the food intake, body mass and blood glucose levels. Importantly, TRF resulted in a significant reduction in plasma testosterone and estradiol levels, delayed nest-building and egg laying, and reduced clutch size. Concurrently, under TRF regimes, we found a significantly lower expression of th and mtr genes linked with motivation and affiliation (but not of dio2, dio3, gnrh1 and gnih genes linked with gonadal maturation) in the hypothalamus, and of star and hook 1 genes in the testes and star, cyp19 and erα genes in the ovary. These results demonstrate the importance of daily food deprivation times on the metabolism and reproduction, and suggest a possible provisioning of energy available from daily feeding for the maintenance of body condition at the expense of reproduction performance in diurnal animals.

Night melatonin levels affect cognition in diurnal animals: Molecular insights from a corvid exposed to an illuminated night environment.

This study investigated the role of nocturnal melatonin secretion in the cognitive performance of diurnal animals. An initial experiment measured the cognitive performance in Indian house crows treated for 11 days with 12 h light at 1.426 W/m2 (∼150 lux) coupled with 12 h of 0.058 W/m2 (∼6-lux) dim light at night (dLAN) or with absolute darkness (0 lux dark night, LD). dLAN treatment significantly decreased midnight melatonin levels and negatively impacted cognitive performance. Subsequently, the role of exogenous melatonin (50 µg; administered intraperitoneally half an hour before the night began) was assessed on the regulation of cognitive performance in two separate experimental cohorts of crows kept under dLAN; LD controls received vehicle. Exogenous melatonin restored its mid-night levels under dLAN at par with those under LD controls, and improved the cognitive performance, as measured in the innovative problem-solving, and spatial and pattern learning-memory efficiency tests in dLAN-treated crows. There were concurrent molecular changes in the cognition-associated brain areas, namely the hippocampus, nidopallium caudolaterale and midbrain. In particular, the expression levels of genes involved in neurogenesis and synaptic plasticity (bdnf, dcx, egr1, creb), and dopamine synthesis and signalling (th, drd1, drd2, darpp32, taar1) were restored to LD control levels in crows treated with illuminated nights and received melatonin. These results demonstrate that the maintenance of nocturnal melatonin levels is crucial for an optimal higher-order brain function in diurnal animals in the face of an environmental threat, such as light pollution.

Prolonged Lockdown due to COVID-19 Alters Sleep-Wake Timings and Negatively Affects Self-esteem, Personality, Depression and Anxiety in College-Going Indian Students.

Purpose: COVID-19 forced the shutdown of colleges and socialization around the world including India and prolonged lockdown could have a significant impact on sleep, mood, emotion and anxiety in students. Here, we designed a survey to assess the effect of lockdown on sleep-wake, self-esteem, depression and anxiety via the survey on 321 Indian college-going students. Methods: We assessed the effect of lockdown on sleep-wake (wake up, get up, bed and sleep timing, total time in bed and sleep duration) and self-esteem and depression on students via various questions. Results: We found that students delayed sleep timing by 1 h in lockdown than pre-lockdown days. Specifically, urban male populations were late sleeper than any other group. However, total sleep duration did not differ between groups. In self-esteem questions, most students agreed that they were of no good, felt nervous, displeased, and frustrated about performance in lockdown. Depression and anxiety questionnaire gave more significant results related to mood and mental health. More than 50% of students agreed that they faced a lack of concentration, had been feeling irritated and angry, felt fatigued and tired, and everything had been a failure during lockdown days. Conclusion: Overall, the survey suggests that lack of social life and prolonged lockdown affect the sleep-wake cycle, self-esteem, anxiety and depression of Indian students. Supplementary Information: The online version contains supplementary material available at 10.1007/s41782-022-00200-9.

Developmental effects of constant light on circadian behaviour and gene expressions in zebra finches: Insights into mechanisms of metabolic adaptation to aperiodic environment in diurnal animals.

A most crucial feature of biological adaptation is the maintenance of a close temporal relationship of behaviour and physiology with prevailing 24-h light-dark environment, which is rapidly changing with increasing nighttime illumination. This study investigated developmental effects of the loss of night on circadian behaviour, metabolism and gene expressions in diurnal zebra finches born and raised under LL, with controls on 12L:12D. Birds under LD were entrained, and showed normal body mass and a significant 24-h rhythm in both activity-rest pattern and mRNA expression of candidate genes that we measured. But, under LL, birds gained weight and accumulated lipid in the liver. Intriguingly, at the end of the experiment, the majority (4/5th) of birds under LL were rhythmic in activity despite arrhythmic expression in the hypothalamus of c-Fos (neuronal activity), Rhodopsin and Mel1-a genes (light perception), and clock genes (Bmal1, Per2 and Rev-erb ß). In peripheral tissues, LL induced variable clock gene expressions. Whereas 24-h mRNA rhythm was abolished for Bmal1 in both liver and gut, it persisted for Per2 and Rev-erb ß in liver, and for Per2 in gut. Further, we found under LL, the loss of 24-h rhythm in hepatic expression of Fasn and Cd36/Fat (biosynthesis and its uptake), and gut expression of Sglt1, Glut5, Cd36 and Pept1 (nutrient absorption) genes. As compared to LD, baseline mRNA levels of Fasn and Cd36 genes were attenuated under LL. Among major transporter genes, Sglt1 (glucose) and Cd36 (fat) genes were arrhythmic, while Glut5 (glucose) and Pept1 (protein) genes were rhythmic but with phase differences under LL, compared to LD. These results demonstrate dissociation of circadian behaviour from clock gene rhythms, and provide molecular insights into possible mechanisms at different levels (behaviour and physiology) that diurnal animals might employ in order to adapt to an emerging overly illuminated-night urban environment.

Effects of timed food availability on reproduction and metabolism in zebra finches: Molecular insights into homeostatic adaptation to food-restriction in diurnal vertebrates.

Food availability affects metabolism and reproduction in higher vertebrates including birds. This study tested the idea of adaptive homeostasis to time-restricted feeding (TRF) in diurnal zebra finches by using multiple (behavioral, physiological and molecular) assays. Adult birds were subjected for 1 week or 3 weeks to food restriction for 4 h in the evening (hour 8-12) of the 12 h light-on period, with controls on ad lib feeding. Birds on TRF showed enhanced exploratory behavior and plasma triglycerides levels, but did not show differences from ad lib birds in the overall food intake, body mass, and plasma corticosterone and thyroxine levels. As compared to ad lib feeding, testis size and circulation testosterone were reduced after first but not after third week of TRF. The concomitant change in the mRNA expression of metabolic and reproductive genes was also found after week 1 of TRF. Particularly, TRF birds showed increased expression of genes coding for gonadotropin releasing hormone (GnRH) in hypothalamus, and for receptors of androgen (AR) and estrogen (ER-alpha) in both hypothalamus and testes. However, genes coding for the deiodinases (Dio2, Dio3) and gonadotropin inhibiting hormone (GnIH) showed no difference between feeding conditions in both hypothalamus and testes. Further, increased Sirt1, Fgf10 and Ppar-alpha, and decreased Egr1 expression in the liver suggested TRF-effects on the overall metabolism. Importantly, TRF-effects on gene expressions by week 1 seemed alleviated to a considerable extent by week 3. These results on TRF-induced reproductive and metabolic effects suggest homeostatic adaptation to food-restriction in diurnal vertebrates.

Sleep in unnatural times: illuminated night negatively affects sleep and associated hypothalamic gene expressions in diurnal zebra finches.

We investigated the effects of exposure at ecologically relevant levels of dim light at night (dLAN) on sleep and the 24 h hypothalamic expression pattern of genes involved in the circadian timing (per2, bmal1, reverb-ß, cry1, ror-α, clock) and sleep regulatory pathways (cytokines: tlr4, tnf-α, il-1ß, nos; Ca2+-dependent pathway: camk2, sik3, nr3a; cholinergic receptor, achm3) in diurnal female zebra finches. Birds were exposed to 12 h light (150 lux) coupled with 12 h of absolute darkness or of 5 lux dim light for three weeks. dLAN fragmented the nocturnal sleep in reduced bouts, and caused sleep loss as evidenced by reduced plasma oxalate levels. Under dLAN, the 24 h rhythm of per2, but not bmal1 or reverb-ß, showed a reduced amplitude and altered peak expression time; however, clock, ror-α and cry1 expressions showed an abolition of the 24 h rhythm. Decreased tlr4, il-1ß and nos, and the lack of diurnal difference in achm3 messenger RNA levels suggested an attenuated inhibition of the arousal system (hence, awake state promotion) under dLAN. Similarly, changes in camk2, sik3 and nr3a expressions suggested dLAN-effects on Ca2+-dependent sleep-inducing pathways. These results demonstrate dLAN-induced negative effects on sleep and associated hypothalamic molecular pathways, and provide insights into health risks of illuminated night exposures to diurnal animals.

Changes in brain peptides associated with reproduction and energy homeostasis: Putative roles of gonadotrophin-releasing hormone-II and tyrosine hydroxylase in determining reproductive performance in response to daily food availability times in diurnal zebra finches.

Previous studies have demonstrated 'quality-quantity' trade-offs with daily food availability times in zebra finches. Compared with food access ad lib., zebra finch pairs with restricted food access for 4 hours in the morning produced poor quality offspring, whereas those with the same food access in the evening produced fewer but better quality offspring. The present study investigated whether food-time-dependent differential effects on reproductive performance involved brain peptides associated with reproduction and energy homeostasis in zebra finches. We measured peptide/protein expression of gonadotrophin-releasing hormone (GnRH)-I, GnRH-II, gonadotrophin-inhibitory hormone (GnIH), tyrosine hydroxylase (TH), neuropeptide Y (NPY), cocaine- and amphetamine regulated transcript (CART) and ZENK (a neuronal activation marker) by immunohistochemistry and mRNA expression of genes coding for the type 2 (DIO2) and type 3 (DIO3) deiodinase by a quantitative polymerase chain reaction in male and female zebra finches that were paired and kept under a 12:12 hour light/dark photocycle at 24 ± 2°C temperature for > 12 months with access to food ad lib., or for only 4 hours in the morning or evening. In both sexes, GnRH-I, DIO2 and DIO3 expression did not differ significantly between the three feeding conditions, although levels showed an overall food effect. However, in males, GnIH expression was significantly higher in evening-fed birds compared to ad lib. fed birds. Interestingly, GnRH-II and TH levels were significantly lower in restricted feeding compared to the ad lib. group and, importantly, GnRH-II and TH-immunoreactivity levels were negatively and positively correlated with egg laying latency and reproductive success (offspring/brood/pair), respectively. At the same time, we found no effect on the hypothalamic expression of orexigenic (NPY) and anorexigenic (CART) peptides, or ZENK protein (ie, the neuronal activity marker). These results suggest the involvement of reproductive neuropeptides, with putative roles for GnRH-II and TH, in the food-time-dependent effect on reproductive performance, albeit with subtle sex differences, in diurnal zebra finches, which possess the ability to reproduce year-round, in a manner similar to other continuously breeding vertebrates.

Changes in the expression of genes involved in DNA methylation and histone modification in response to daily food availability times in zebra finches: epigenetic implications.

We hypothesised that daily food availability times serve as an 'epigenetic' factor and affect reproductive physiology in continuously reproducing species. This we tested by measuring mRNA expression of genes coding for enzymes involved in DNA methylation-demethylation (dnmt, tet) and histone modification (hat1, hdac) in the hypothalamus, liver and gonads of male and female zebra finches that were paired for a year under 12 h light:12 h dark conditions with food availability restricted to 4 h in the morning (morning FA group) or evening (evening FA group), with controls provided with food ad libitum The overall hypothalamic and hepatic expression patterns of hat1 and hdac were similar but those of dnmt and tet were different between males and females. Irrespective of the timing of food availability, both hat1 and hdac mRNA levels were increased in the hypothalamus, but not in the liver, in which hat1 mRNA levels were increased in the morning FA group. While hypothalamic tet levels were higher in evening FA males, hepatic tet levels were higher in morning FA birds (tet1, only males). Gonadal expression levels similarly varied and showed sex differences. Histone-modifying genes did not show food availability effects, except for elevated testicular hdac3 levels. Similarly, testicular dnmt3b and tet2 mRNA levels were increased and decreased in morning and evening FA groups, respectively, whereas ovarian dnmt1 and tet2 levels were reduced in morning FA and tet1 levels were reduced in evening FA groups. The present results suggest that an enforced daily feeding schedule in the long term could serve as a conditioning environment that shapes overall hypothalamic regulation, and liver and gonadal function at the epigenetic level in diurnal vertebrates.

Developmental effects of daily food availability times on song behaviour and neuronal plasticity of song-control system in male zebra finches.

Food availability is a major ecological factor and affects body condition and sexual traits. Here, we investigated whether males' song behaviour, a trait for female mate choice, was sensitive to the food availability period and its timing in songbirds. We manipulated daily food availability to 4 h in the morning or evening, with controls on food ad libitum, and assessed its effects on song behaviour and forebrain song control system in male zebra finches that were held as adult (parent) or offspring (since birth) at 24 ± 2 °C under 12 h daily photoperiod. Food restriction significantly affected both temporal and spectral features of daily song in offspring, not the parent. In offspring, we found reduced mesor (mean 24-h levels), attenuated amplitude (daily maxima relative to mesor) and altered acrophase (estimated time of daily maxima) of 24-h rhythm, and reduced motif length (in morning-fed), per motif unique syllables and an enhanced song pitch (in evening-fed). There was also a positive correlation of motif length with cheek patch and plasma testosterone levels, and of per motif syllables with cheek patch and daily activity levels in offspring. Among main song controlling forebrain nuclei, LMAN and HVC were reduced in size, and Area X and HVC showed decreased neuronal recruitment in offspring on food restrictions. These results demonstrate the importance of daily food availability and its timing in determining males' sexual signals, and support growing evidence that among vertebrates well-fed males contain reproductive traits that females use for its mate choice.

Dissociation of circadian activity and singing behavior from gene expression rhythms in the hypothalamus, song control nuclei and cerebellum in diurnal zebra finches.

Under periodic day-night environment, most circadian functions maintain a close phase relationship relative to each other, suggesting a common circadian pacemaker control of different overt rhythms. In birds, this seems highly unlikely, given multioscillatory nature of the circadian pacemaker and downstream generation of several circadian behaviors. We hypothesized the dissociation of overt rhythms from circadian gene oscillations, if the two were loosely coupled, under an aperiodic light condition. We tested this in daily rhythms in singing, activity and clock gene expressions in adult male zebra finches (Taeniopygia guttata) that were born and raised under the constant light (LL; 24L:0D), with controls on an LD cycle (12L: 12D). Particularly, we monitored daily pattern of singing and activity behavior, and measured 24 h mRNA expression of immediate early gene (c-Fos), clock genes (Bmal1, Per2 and Rev-erb ß) and epigenetic marker genes (Dnmt3b and Tet2) in the hypothalamus, and of clock genes and genes coding for the aromatase (Arom), androgen receptor (Ar) and dopamine receptor (Drd2) in the song control nuclei (Area X and HVC) and cerebellum (motor control region). We found persistence of daily rhythms in activity and singing in all birds under LD, but in only 70% (14/20) birds under LL; thus, both behaviors were arrhythmic in 30% (6/20) birds) under LL. The overall song quality was also declined under LL. The clock genes showed daily rhythms in the hypothalamus, song control nuclei (except Per2 in Area X) and cerebellum under LD, although with differences in peak expression times; however, there was loss of rhythmicity in clock genes (except Bmal1 in Area X and HVC) under LL. We also found daily Ar mRNA rhythm in the Area X and cerebellum under LD. These results demonstrate for the first time the persistence of clock gene oscillations in the song control brain regions and show the dissociation of circadian behavior from genetic oscillations in relation to an imposed light environment.

Light at night affects hippocampal and nidopallial cytoarchitecture: Implication for impairment of brain function in diurnal corvids.

Our previous studies have shown that light at night (LAN) impaired cognitive performance and affected neurogenesis and neurochemistry in the cognition-associated brain regions, particularly the hippocampus (HP) and lateral caudal nidopallium (NCL) of Indian house crows (Corvus splendens). Here, we examined the cytoarchitecture and mapped out the morphology of neurons and glia-neuron density in HP and NCL regions of crows that were first entrained to 12-hr light (LL): 12-hr darkness (LD) and then exposed to the light regime in which 12-hr darkness was either replaced by daytime light (i.e., constant light, LL) or by dim light (i.e., dim light at night, dLAN), with controls continued on LD 12:12. Compared with LD, there was a significant decrease in the soma size, suggesting reduced neuronal plasticity without affecting the neuronal density of both HP and NCL of crows under LL and dLAN conditions. In parallel, we found a reduced number of glia cells and, hence, decreased glia-neuron ratio positively correlated with soma size in both, HP and NCL regions. These results for the first time demonstrate LAN-induced negative effects on the brain cytoarchitecture of a diurnal species and give insight for possible influence on the brain health and functions in animals including humans that might be inadvertently exposed to LAN in an emerging night-illuminated urban environment.

Illuminated night alters hippocampal gene expressions and induces depressive-like responses in diurnal corvids.

Artificial light at night induces circadian disruptions and causes cognitive impairment and mood disorders; yet very little is known about the neural and molecular correlates of these effects in diurnal animals. We manipulated the night environment and examined cellular and molecular changes in hippocampus, the brain region involved in cognition and mood, of Indian house crows (Corvus splendens) exposed to 12 hr light (150 lux): 12 hr darkness (0 lux). Diurnal corvids are an ideal model species with cognitive abilities at par with mammals. Dim light (6 lux) at night (dLAN) altered daily activity:rest pattern, reduced sleep, and induced depressive-like responses (decreased eating and self-grooming, self-mutilation, and reduced novel object exploration); return to an absolute dark night reversed these negative effects. dLAN suppressed nocturnal melatonin levels; however, diurnal corticosterone levels were unaffected. Concomitant reduction of immunoreactivity for DCX and BDNF suggested dLAN-induced suppression of hippocampal neurogenesis and compromised neuronal health. dLAN also negatively influenced hippocampal expression of genes associated with depressive-like responses (bdnf, il-1ß, tnfr1, nr4a2), but not of those associated with neuronal plasticity (egr1, creb, syngap, syn2, grin2a, grin2b), cellular oxidative stress (gst, sod3, cat1) and neuronal death (caspase2, caspase3, foxo3). Furthermore, we envisaged the role of BDNF and showed epigenetic modification of bdnf gene by decreased histone H3 acetylation and increased hdac4 expression under dLAN. These results demonstrate transcriptional and epigenetic bases of dLAN-induced negative effects in diurnal crows, and provide insights into the risks of exposure to illuminated nights to animals including humans in an urban setting.

Constant light environment suppresses maturation and reduces complexity of new born neuron processes in the hippocampus and caudal nidopallium of a diurnal corvid: Implication for impairment of the learning and cognitive performance.

Periodic day-night environment shapes the temporal pattern in the behaviour and physiology (e.g. 24-h activity-rest and sleep-wake cycles) and the advanced brain function, such as learning, memory and decision making. In a previous study, we showed the abolition of 24-h rhythm in the activity-rest pattern, and an attenuated cognitive performance in diurnal Indian house crows (Corvus splendens) under constant light (no-night; LL) environment. Present study extended this, and investigated LL-induced effects on the neurogenesis (birth, maturation and neurite complexity of new born neurons) in the hippocampus and caudal nidopallium, the brain regions directly associated with learning and cognition in birds. We performed immunohistochemistry of doublecortin (DCX; a neurogenesis marker) and tyrosine hydroxylase (TH, a key enzyme of the dopamine biosynthesis) in the brain section containing hippocampus or caudal nidopallium of Indian house crows exposed for 2 weeks to LL, with controls maintained under 12L:12D. As expected, crows showed arrhythmicity with a significantly reduced rest period in the 24-h activity-rest pattern, and a decreased cognitive performance when tested for the spatial and pattern association learning tasks under LL. Importantly, there was a significant decrease in DCX-immunoreactive (ir) cells and, as shown by Sholl analysis, in the complexity of DCX-ir neurites in both, the hippocampus and caudal nidopallium of crows under LL, as compared to those under 12L:12D. The anatomical proximity of DCX-ir neurons with TH-ir fibers suggested a functional association of the new born hippocampal and caudal nidopallial neurons with the learning, and perhaps cognition in Indian house crows. These results give insights into possible impact of the loss of night on brain health and functions in an emerging ecosystem in which other diurnal species including humans may be inadvertently exposed to an illuminated night, such as in an overly lighted metropolitan urban habitat.