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Conversations with a Neuron, Volume 4

The link between light and mood-related disorders

A new study sheds light on the underlying mechanisms of how light can affect mood-related behavior within a population of mice.

Author: Shiva Chhetri

Neuroanatomy

Introduction

Although there is wide belief and understanding regarding the positive effects of light therapy for certain mood-related behaviors, the underlying mechanisms are not well understood. Therefore by taking a closer look at the suprachiasmatic nuclei (SCN) and other functional genes such as period genes (Per1&2) as well as cryptochrome genes (Cry1&2), there is a deeper approach to understanding this conventional mode of therapy. In a paper recently published in PLOS genetics, Olejniczak and Ripperger investigate how regions such as the lateral habenula (LHb) area of the brain and other genes help in mood regulation. This is necessary as the researchers point out, there is still a lack of understanding as to the inner workings of the LHb that leads to this correlation. As the study notes, this lack of proper understanding also branches into the molecular mechanisms regarding light's ability to elicit beneficial effects on mood-related behaviors. As such the findings of this study are quite notable considering how they support the notion that Per 1 gene within the LHb aids in the expression of particular mechanisms in relation to light stimuli. These findings are necessary as they provide an opportunity to allow for a first glimpse into potential molecule pathways that are related to this gene as well as other synergistic genes. The implications of this study are worth mentioning as malfunctioning or disruption of the circadian rhythm system can result in various pathologies in mammals including obesity, cancer, and neurological dysfunctions (Roenneberg, 2016). In conjunction, it is necessary to understand the circadian rhythm and light as it is an important system for the mammalian body as its prime goal is to maintain synchronicity and homeostasis. A good example of this is how it has been shown in cyanobacteria & humans how the circadian rhythm allows for them to respond appropriately to the daily light-dark cycle (Rosbash, 2009). This response has been shown in how the body begins producing particular neurotransmitters such as melatonin, produced by Pineal gland (Gonzalez, 2008). In association, it is also purported by the researchers that getting a better understanding of how the circadian clock is impacted by exposure to light will allow for better understanding of subjects such as sleep and mood-related disorders. As pointed out by the researchers, there have been prior studies conducted in regards to how the LHb area aids in mood regulation. One such study on this subject matter has pointed out how “light modulated LHb activity via M4-type melanopsin-expressing retinal ganglion cells allow for regulating depressive behaviors (Huang L, 2019)”. Although what is different about this study is how this study aims to also investigate whether Per 1 is induced within the LHb via the “M4-type melanopsin-expressing” in regulating depressive behaviors. 

Figure 1: A figure showing the suspected pathway between light stimuli and amelioration of depressive symptoms. From left to right. Light stimulus (Light). Example of a mammalian eyeball, the particular visual system involved in this study is the retina (Retina). Thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL). Lateral Habenula (LHb). Ventral tegmental area (VTA). Dorsal raphe nuclei (DRN). Courtesy of Huang and Xi et al. Neuron.Science-Direct.Volume 102.Issue1,3 April 2019. Pages 128-142.e8.
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Methods 

The methods used for this study included mice which were kept in 12 hour light and 12 hour dark cycles with appropriate food and water. In addition, the study made use of zeitgeber time, a form of measurement that is related to measuring time of mechanisms within the body that run on a 24 hour time scale (Albrecht, 1997). Other factors also included knock-out mice that did not have the Per 1 gene, light pulse experiments, behavioral testing (mood/etc), sucrose preference test, brain region isolation (mostly for brain section analysis), immunostaining, quantitative polymerase chain reaction (qPCR) analysis, transcriptome analysis, cell cultures, protein isolation from brain tissue, western blots (for proteins), in situ hybridization, and sleep assessment analysis. 

 

Results

The results found by the researchers at the end of the study seemed to align with what was proposed within the introduction of the paper. Relevant findings included how light-mediated induction of the gene Per 1 in the lateral habenula (Lhb) seems to be involved in the antidepressant effects of light therapy. In relation to this, the mice populations used showed that there was a sex-related discrepancy wherein light treatment during the late part of the dark phase (Zieitberger time-22) was more effective in females than male mice. However, this same sex related discrepancy oddly does not seem to be present in humans with seasonal affective depression in response to light therapy (Wirz-Justice, 2013). This seemed to be notable when considering that in humans rates of depression are higher in the female gender in comparison to that of males(Leibenluft, 1995). The paper also highlights that although mood-related behaviors are a complex trait, it was found that in certain mice populations (Per 1 knock-out) that the lack of Per 1 resulted in the absence of a light response and also seemed to increase immobility time. Furthermore, in these populations, it was shown that the LHb was not activated by a dark-light transition. These results led the researchers to predict that the notion that Per 1 participates in mood-related behaviors was supported via the findings by the study. Overall, it was concluded that the study provides evidence which supports the notion that there is relation between light and mood-related behaviors which involves the clock gene Per 1 and that induction of this gene in neurons in the area of the LHb plays an important role. 

 

Discussion

As a student this study is very fascinating as it is based on the study of mood-related disorders and mechanisms that directly affect the circadian rhythm in mammals. Personally, subjects such as depression, happiness, and sleep hygiene are not things that affect just me but many other of my peers who are students. Based on personal empirical evidence, there is little doubt as to the importance of this study. A desirable outcome for this study is for there to be furthered interest regarding this topic and potential techniques to combat mood-related disorders in humans. 

 

[+] References

1.

Roenneberg T, Merrow M. The Circadian Clock and Human Health. Curr Biol. 2016;26(10):R432–43. pmid:27218855

 

2.

Rosbash M. The implications of multiple circadian clock origins. PLoS Biol. 2009;7(3):e62. pmid:19296723

 

3.

Gonzalez MM, Aston-Jones G. Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats. Proc Natl Acad Sci U S A. 2008;105(12):4898–903. pmid:18347342

 

4.

Albrecht U, Sun ZS, Eichele G, Lee CC. A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light. Cell. 1997;91(7):1055–64. Pmid:9428527

 

5.

Wirz-Justice A, Benedetti F, Terman M. Chronotherapeutics for affective disorders: a clinician’s manual for light and wake therapy. 2nd, rev. ed. Basel; New York: Karger; 2013. xii, 124 p. P.

 

6.

Leibenluft E, Hardin TA, Rosenthal NE. Gender differences in seasonal affective disorder. Depression. 1995;3:13–9.

7.

Olejniczak, I., Ripperger, J. A., Sandrelli, F., Schnell, A., Mansencal-Strittmatter, L., Wendrich, K., Hui, K. Y., Brenna, A., Fredj, N. B., & Albrecht, U. (2021, July 8). Light affects behavioral despair involving the clock gene period 1. PLOS Genetics. Retrieved April 26, 2022, from https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1009625  

 

8.

Huang, L., Xi, Y., Peng, Y., Yang, Y., Huang, X., Fu, Y., Tao, Q., Xiao, J., Yuan, T., An, K., Zhao, H., Pu, M., Xu, F., Xue, T., Luo, M., So, K.-F., & Ren, C. (2019, February 19). A visual circuit related to habenula underlies the antidepressive effects of light therapy. Neuron. Retrieved April 25, 2022, from https://www.sciencedirect.com/science/article/pii/S0896627319300649