Nurr1 deficiency shortens free running period, enhances photoentrainment to phase advance, and disrupts circadian cycling of the dopamine neuron phenotype

Partington, H.; Nutter, Jennifer M.; Eells, Jeffrey B.

doi:10.1016/j.bbr.2021.113347

Cited by 3 publications

(12 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, mice with Rev-Erbα gene deleted have higher DA release in the nucleus accumbens (NAc) (Chung et al, 2014). It appears that Nurr1 competes with Rev-Erbα to promote TH expression; consistent with this mice heterozygous for Nurr1 deletion have altered circadian phenotypes (Partington et al, 2021). In rodents, extracellular DA levels, i.e., "dopamine tone, " in the striatum is at their highest during the night and lowest during the day; this is mediated by the activity of the dopamine transporter (DAT or Slc6a3), which is responsible for reuptake of DA at synapse-a primary means of terminating DA signals (Ferris et al, 2014).…”

Section: Dopamine Rhythms and Their Influence On Circadian Behaviorssupporting

confidence: 60%

Dopamine systems and biological rhythms: Let’s get a move on

Tang

Assali

Güler

et al. 2022

Front. Integr. Neurosci.

View full text Add to dashboard Cite

How dopamine signaling regulates biological rhythms is an area of emerging interest. Here we review experiments focused on delineating dopamine signaling in the suprachiasmatic nucleus, nucleus accumbens, and dorsal striatum to mediate a range of biological rhythms including photoentrainment, activity cycles, rest phase eating of palatable food, diet-induced obesity, and food anticipatory activity. Enthusiasm for causal roles for dopamine in the regulation of circadian rhythms, particularly those associated with food and other rewarding events, is warranted. However, determining that there is rhythmic gene expression in dopamine neurons and target structures does not mean that they are bona fide circadian pacemakers. Given that dopamine has such a profound role in promoting voluntary movements, interpretation of circadian phenotypes associated with locomotor activity must be differentiated at the molecular and behavioral levels. Here we review our current understanding of dopamine signaling in relation to biological rhythms and suggest future experiments that are aimed at teasing apart the roles of dopamine subpopulations and dopamine receptor expressing neurons in causally mediating biological rhythms, particularly in relation to feeding, reward, and activity.

show abstract

Section: Dopamine Rhythms and Their Influence On Circadian Behaviorssupporting

confidence: 60%

Dopamine systems and biological rhythms: Let’s get a move on

Tang

Assali

Güler

et al. 2022

Front. Integr. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Dopaminergic control was next assessed in relation to light‐cycle regulation of physical activity as a measure of the role of dopamine in circadian control (Grippo & Güler, 2019; Mendoza & Challet, 2014; Partington et al, 2021). The activity was monitored in light‐controlled housing chambers containing running wheels.…”

Section: Resultsmentioning

confidence: 99%

“…The cycle was then shifted 6 h earlier with a dark cycle from 1330 to 0130 to emulate jet lag. Mice were then maintained in 24-h darkness to determine the free-running period ( Partington et al, 2021 ). All activities within the cabinets were monitored and quantified using ClockLab software (Actimetrics, Wilmette, IL).…”

Section: Methodsmentioning

confidence: 99%

“…The number of days required for the animals to consistently initiate wheel running, at least 5 h prior to the jetlag initiation, was used to determine days to entrainment. important for the dopaminergic activity of a neuron and for the sensitivity to altered photoentrainment (Partington et al, 2021).…”

Section: Dopaminergic Acsl6 Is Required For Recovery From Photoperiod...mentioning

confidence: 99%

“…ACSL6 knockout ( Acsl6 −/− ) mice demonstrate that hyperlocomotion behavior reflected by increased travel time, speed, and fewer freezing bouts observed across several distinct observational testing scenarios ( Fernandez et al, 2018 , 2021 ; Fernandez & Ellis, 2020 ). Dopamine is well established to regulate locomotion ( Beninger, 1983 ), thus, herein, we questioned the role of ACSL6-regulated fatty acid metabolism in dopamine metabolism and dopaminergic control of motor activity and circadian rhythms ( Partington et al, 2021 ). We confirmed the expression of ACSL6 in dopaminergic neurons and showed that the germline deletion of ACSL6 resulted in reduced levels of membrane polyunsaturated fatty acids in brain regions enriched with dopaminergic innervations, along with altered striatal dopamine turnover.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lipid metabolism in dopaminergic neurons influences light entrainment

Fernandez

Wilson

Diaz

et al. 2023

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

Dietary lipids, particularly omega‐3 polyunsaturated fatty acids, are speculated to impact behaviors linked to the dopaminergic system, such as movement and control of circadian rhythms. However, the ability to draw a direct link between dopaminergic omega‐3 fatty acid metabolism and behavioral outcomes has been limited to the use of diet‐based approaches, which are confounded by systemic effects. Here, neuronal lipid metabolism was targeted in a diet‐independent manner by manipulation of long‐chain acyl‐CoA synthetase 6 (ACSL6) expression. ACSL6 performs the initial reaction for cellular fatty acid metabolism and prefers the omega‐3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). The loss of Acsl6 in mice (Acsl6−/−) depletes neuronal membranes of DHA content and results in phenotypes linked to dopaminergic control, such as hyperlocomotion, impaired short‐term spatial memory, and imbalances in dopamine neurochemistry. To investigate the role of dopaminergic ACSL6 on these outcomes, a dopaminergic neuron‐specific ACSL6 knockout mouse was generated (Acsl6DA−/−). Acsl6DA−/− mice demonstrated hyperlocomotion and imbalances in striatal dopamine neurochemistry. Circadian rhythms of both the Acsl6−/− and the Acsl6DA−/− mice were similar to control mice under basal conditions. However, upon light entrainment, a mimetic of jet lag, both the complete knockout of ACSL6 and the dopaminergic‐neuron‐specific loss of ACSL6 resulted in a longer recovery to entrainment compared to control mice. In conclusion, these data demonstrate that ACSL6 in dopaminergic neurons alters dopamine metabolism and regulation of light entrainment suggesting that DHA metabolism mediated by ACSL6 plays a role in dopamine neuron biology.

show abstract

The circadian system: A neglected player in neurodevelopmental disorders

Bouteldja,

Penichet,

Srivastava

et al. 2024

Eur J of Neuroscience

View full text Add to dashboard Cite

Patients with neurodevelopmental disorders, such as autism spectrum disorder, often display abnormal circadian rhythms. The role of the circadian system in these disorders has gained considerable attention over the last decades. Yet, it remains largely unknown how these disruptions occur and to what extent they contribute to the disorders' development. In this review, we examine circadian system dysregulation as observed in patients and animal models of neurodevelopmental disorders. Second, we explore whether circadian rhythm disruptions constitute a risk factor for neurodevelopmental disorders from studies in humans and model organisms. Lastly, we focus on the impact of psychiatric medications on circadian rhythms and the potential benefits of chronotherapy. The literature reveals that patients with neurodevelopmental disorders display altered sleep–wake cycles and melatonin rhythms/levels in a heterogeneous manner, and model organisms used to study these disorders appear to support that circadian dysfunction may be an inherent characteristic of neurodevelopmental disorders. Furthermore, the pre‐clinical and clinical evidence indicates that circadian disruption at the environmental and genetic levels may contribute to the behavioural changes observed in these disorders. Finally, studies suggest that psychiatric medications, particularly those prescribed for attention‐deficit/hyperactivity disorder and schizophrenia, can have direct effects on the circadian system and that chronotherapy may be leveraged to offset some of these side effects. This review highlights that circadian system dysfunction is likely a core pathological feature of neurodevelopmental disorders and that further research is required to elucidate this relationship.

show abstract

Nurr1 deficiency shortens free running period, enhances photoentrainment to phase advance, and disrupts circadian cycling of the dopamine neuron phenotype

Cited by 3 publications

References 69 publications

Dopamine systems and biological rhythms: Let’s get a move on

Dopamine systems and biological rhythms: Let’s get a move on

Lipid metabolism in dopaminergic neurons influences light entrainment

The circadian system: A neglected player in neurodevelopmental disorders

Contact Info

Product

Resources

About