scholarly journals Light affects behavioral despair involving the clock gene Period 1

2020 ◽  
Author(s):  
Iwona Olejniczak ◽  
Jürgen A. Ripperger ◽  
Federica Sandrelli ◽  
Anna Schnell ◽  
Laureen Mansencal-Strittmatter ◽  
...  
Keyword(s):  
Brain Region ◽  
Clock Gene ◽  
Dopaminergic System ◽  
Light Therapy ◽  
Suprachiasmatic Nuclei ◽  
Lateral Habenula ◽  
Knock Out ◽  
Environmental Light ◽  
And Behavior ◽  
G Protein Coupled

AbstractLight at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle. Here we provide evidence that light affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors. A light pulse given at ZT22 to wild type mice caused profound changes of gene expression in the mesolimbic dopaminergic system including the nucleus accumbens (NAc). Sensory perception of smell and G-protein coupled receptor signaling was affected the most in this brain region. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene induction in the brain. Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on signaling mechanisms in the mesolimbic dopaminergic system.

scholarly journals Light affects behavioral despair involving the clock gene Period 1

PLoS Genetics ◽  
2021 ◽  
Vol 17 (7) ◽  
pp. e1009625
Author(s):  
Iwona Olejniczak ◽  
Jürgen A. Ripperger ◽  
Federica Sandrelli ◽  
Anna Schnell ◽  
Laureen Mansencal-Strittmatter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Dopaminergic System ◽  
Light Therapy ◽  
Lateral Habenula ◽  
Knock Out ◽  
Beneficial Effects ◽  
Environmental Light ◽  
And Behavior ◽  
G Protein Coupled

Light at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle. Here we provide evidence that light at zeitgeber time (ZT) 22 affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors. We show that complete deletion of Per1 in mice led to depressive-like behavior and loss of the beneficial effects of light on this behavior. In contrast, specific deletion of Per1 in the region of the LHb did not affect mood-related behavior, but suppressed the beneficial effects of light. RNA sequence analysis in the mesolimbic dopaminergic system revealed profound changes of gene expression after a light pulse at ZT22. In the nucleus accumbens (NAc), sensory perception of smell and G-protein coupled receptor signaling were affected the most. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene expression in the brain. Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on mood-related behavior and signaling mechanisms in the mesolimbic dopaminergic system.

Effects of Homocysteine on the Dopaminergic System and Behavior in Rodents

2005 ◽  
Vol 26 (3) ◽  
pp. 361-371 ◽  
Author(s):  
E LEE ◽  
H CHEN ◽  
K SOLIMAN ◽  
C CHARLTON
Keyword(s):  
Dopaminergic System ◽  
And Behavior

PARENTAL REPORTS OF SEASONAL MOOD AND BEHAVIOR CHANGES IN CHILDREN

PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. A70-A70
Author(s):  
Mary A. Carskadon ◽  
Christine Acebo
Keyword(s):  
Response Rate ◽  
Light Therapy ◽  
The United States ◽  
Therapeutic Benefit ◽  
Behavior Changes ◽  
Regional Effects ◽  
Parental Reports ◽  
And Behavior ◽  
Potential Therapeutic Benefit ◽  
Careful Assessment

Objective: The chief purpose of this study was to investigate the nature and prevalence of children's seasonal symptoms. Method: Parental reports of seasonal changes in six mood or behavioral symptoms (sleeping, eating, irritability, energy, withdrawal, and sadness) were surveyed for children living across the United States. The sample included 892 girls (mean age = 10.5 ± 1.0 years) and 788 boys (mean age = 10.6 ± 0.9 years), with a response rate of 46% for girls' parents and 39% for boys' parents. Results: At least one winter recurring symptom was reported in 48.5% of children, as compared with 91% in fall and 10.8% in spring. Winter symptoms were reported equally in girls and boys with one exception ("is tired"); age effects were found for three symptoms only in girls ("sleeps more," "is tired," and "withdraws"). Regional effects showed more winter symptoms reports in northern zones than in southern zones. Conclusions: Given the potential therapeutic benefit of light therapy in children with seasonal patterns, careful assessment of seasonality is merited for children with winter mood and behavior problems.

scholarly journals LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
Chiara Camillo ◽  
Nicola Facchinello ◽  
Giulia Villari ◽  
Giulia Mana ◽  
Noemi Gioelli ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Focal Adhesion ◽  
Nuclear Localization ◽  
Molecular Mechanisms ◽  
Transcriptional Regulators ◽  
Dependent Manner ◽  
Knock Out ◽  
Dynamic Modulation ◽  
Differential Control ◽  
G Protein Coupled

Dynamic modulation of endothelial cell-to-cell and cell–to–extracellular matrix (ECM) adhesion is essential for blood vessel patterning and functioning. Yet the molecular mechanisms involved in this process have not been completely deciphered. We identify the adhesion G protein–coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of endothelial cell (EC) adhesion and barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM contacts, signals through cAMP/Rap1, and inhibits focal adhesion (FA) formation and nuclear localization of YAP/TAZ transcriptional regulators, while promoting tight junction (TJ) assembly. ECs also express an endogenous LPHN2 ligand, fibronectin leucine-rich transmembrane 2 (FLRT2), that prevents ECM-elicited EC behaviors in an LPHN2-dependent manner. Vascular ECs of lphn2a knock-out zebrafish embryos become abnormally stretched, display a hyperactive YAP/TAZ pathway, and lack proper intercellular TJs. Consistently, blood vessels are hyperpermeable, and intravascularly injected cancer cells extravasate more easily in lphn2a null animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.

3-Iodothyronamine Induces Diverse Signaling Effects at Different Aminergic and Non-Aminergic G-Protein Coupled Receptors

2019 ◽  
Vol 128 (06/07) ◽  
pp. 395-400 ◽  
Author(s):  
Heike Biebermann ◽  
Gunnar Kleinau
Keyword(s):  
Body Temperature ◽  
G Protein ◽  
Intracellular Signaling ◽  
Serotonin Receptor ◽  
Fine Tuning ◽  
Specific Cell ◽  
Knock Out ◽  
Alpha2 Adrenoceptor ◽  
Knock Out Mice ◽  
G Protein Coupled

AbstractThe thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts diverse physiological reactions such as a decrease of body temperature, and negative inotropic and chronotropic effects. This observed pleomorphic effect in physiology can be barely explained by interaction with only one target protein such as the trace-amine receptor 1 (TAAR1), a class A G-protein coupled receptor (GPCR). Moreover, Taar1 knock-out mice still react to 3-T1AM through physiological responses with a rapid decrease in body temperature. These facts propelled our group and others to search for further targets for this molecule.The group of TAARs evolved early in evolution and, according to sequence similarities, they are closely related to adrenoceptors and other aminergic receptors. Therefore, several of these receptors were characterized by their potential to interplay with 3-T1AM. Indeed, 3-T1AM acts as a positive allosteric modulator on the beta2-adrenoceptor (ADRB2) and as a biased agonist on the serotonin receptor 1B (5HT1b) and the alpha2-adrenoceptor (ADRA2A). In addition, 3-T1AM was reported to be a weak antagonist at a non-aminergic muscarinic receptor (M3).These findings impressively reflect that such trace amines can unselectively and simultaneously function at different receptors expressed by one cell or at different tissues. In conclusion, the role of 3-T1AM is hypothesized to concert the fine-tuning of specific cell reactions by the accentuation of certain pathways dependent on distinct receptors. 3-T1AM acts as a regulator of signals by blocking, modulating, or inducing simultaneously distinct intracellular signaling cascades via different GPCRs.

IMPAIRED EXPRESSION OF THEmPer2CIRCADIAN CLOCK GENE IN THE SUPRACHIASMATIC NUCLEI OF AGING MICE

2001 ◽  
Vol 18 (3) ◽  
pp. 559-565 ◽  
Author(s):  
Heike Weinert ◽  
Dietmar Weinert ◽  
Irina Schurov ◽  
Elizabeth S. Maywood ◽  
Michael H. Hastings
Keyword(s):  
Clock Gene ◽  
Suprachiasmatic Nuclei

scholarly journals Stress transforms lateral habenula reward responses into punishment signals

2019 ◽  
Vol 116 (25) ◽  
pp. 12488-12493 ◽  
Author(s):  
Steven J. Shabel ◽  
Chenyu Wang ◽  
Bradley Monk ◽  
Sage Aronson ◽  
Roberto Malinow
Keyword(s):  
Risk Factor ◽  
Neuronal Activity ◽  
Negative Feedback ◽  
Brain Region ◽  
Acute Stress ◽  
Major Risk Factor ◽  
Neural Signals ◽  
Lateral Habenula ◽  
Positive And Negative Feedback ◽  
Negative Expectations

Neuronal activity in the lateral habenula (LHb), a brain region implicated in depression [C. D. Proulx, O. Hikosaka, R. Malinow, Nat. Neurosci. 17, 1146–1152 (2014)], decreases during reward and increases during punishment or reward omission [M. Matsumoto, O. Hikosaka, Nature 447, 1111–1115 (2007)]. While stress is a major risk factor for depression and strongly impacts the LHb, its effect on LHb reward signals is unknown. Here we image LHb neuronal activity in behaving mice and find that acute stress transforms LHb reward responses into punishment-like neural signals; punishment-like responses to reward omission also increase. These neural changes matched the onset of anhedonic behavior and were specific to LHb neurons that distinguished reward and its omission. Thus, stress distorts LHb responsivity to positive and negative feedback, which could bias individuals toward negative expectations, a key aspect of the proposed pathogenesis of depression [A. T. Beck, Depression: Clinical, Experimental, and Theoretical Aspects, sixth Ed (1967)].

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