User:Doualex/Joanna Meijer

Light responses of the mammalian circadian system.
Meijer’s work contributed the neural and molecular characterization of light responses in the mammalian circadian system. Using electrophysiological recordings of the suprachiasmatic nuclei (SCN) in rodents, Meijer’s early studies produced detailed descriptions of the prevalence and properties of visual SCN neurons activated by retinal light exposure (1). Meijer went on to characterize the baseline and light-induced activity of the mammalian SCN through long-term recordings in freely moving rats, which helped establish the ability of the SCN to produce circadian rhythms in neural activity in vivo (3).

Studying light input to the SCN, Meijer demonstrated that glutamate injections in the SCN produce phase shifts in the circadian activity rhythms of hamsters similar to those induced by light exposure, suggesting the role of glutamate in mediating photic entrainment (2). Building upon this finding, Meijer later identified the presence of glutamate receptors within the retinohypothalamic tract of brown Norwegian rats through the use of immunogold labeling, providing molecular evidence for the role of glutamate as a neurotransmitter that mediates photic signals to the circadian clock (4).

Probing the role of classical photoreceptors in photic entrainment, Meijer’s lab demonstrated that light-dependent activation of the SCN was retained in mice lacking melanopsin (Opn4-/-) but strongly attenuated in mice lacking rods and cones (rd/rd cl) (4). These results provided evidence for the role of classical photoreceptors in transmitting light information to the SCN, which implicates photopigments beyond melanopsin in modulating the mammalian circadian clock.

Clinical implications of circadian biology.
A major goal of Meijer’s current research is to understand the health consequences of circadian disruptions (5). Meijer contributed to studies demonstrating the regulation of monoamine oxidase A by the circadian clock proteins BMAL1, NPAS2, and PER2 in mice (6). This finding established a molecular connection between circadian rhythms, dopamine metabolism, and mood-related behavior, which implicates circadian disruptions in mood regulation (6).

Through electrical recordings in mice, Meijer’s group showed that circadian rhythms in the SCN exhibit desynchronization and reduced amplitude in the brain with increasing age, which has been associated with amyloid aggregation in Alzheimer’s disease (7). These findings have provided evidence that the circadian dysfunctions observed in Alzheimer’s disease result from SCN deterioration (8).

Research on circadian energy metabolism in the Meijer lab helped establish the detrimental effects of a high-fat diet on metabolic gene expression in liver and adipose tissue, supporting the role of circadian alterations in the development of insulin resistance and obesity (9). Additionally, mouse SCN lesion experiments performed in the Meijer lab identified disruptions in circadian glucose homeostasis rhythms, corroborating observations in whole-animal knockout studies of circadian genes (9).

Studying the circadian response to sleep deprivation, Meijer’s group obtained the first evidence that sleep centers in the brain directly regulates activity of the SCN (11). By monitoring SCN activity and sleep phase in live mice, Meijer and colleagues demonstrated that slow-wave activity during non-rapid eye movement (NREM) sleep was found to be negatively associated with SCN activity (11). Furthermore, the transition between NREM and rapid-eye movement (REM) sleep was found to correspond to alterations in SCN firing patterns (10). In subsequent experiments, sleep deprivation in rats was found to decrease the amplitude of SCN activity for a minimum of 6 hours, which is suggested to underlie the disruptions in sleep timing and quality observed in elderly individuals and patients with neurodegenerative disorders (10).

Academic Positions

 * 2007-Present: Full Professor, Department of Physiology, LUMC, Leiden, The Netherlands. (5)
 * 2013-Present: Visiting Professor, Nuffield Department of Opthalmology and Clinical Neuroscience, Oxford University, GB. (5)
 * 2001-2007: Associate Professor, Department of Physiology, LUMC, Leiden, The Netherlands. (5)
 * 1992-2001: Assistant Professor, Department of Physiology, LUMC, Leiden, The Netherlands. (5)
 * 2014-Present: Member of the Royal Dutch Society of Sciences (5)
 * 2012: Elected Member at Large of the Society for Biological Rhythm Research.  (5)
 * 1989: Fellowship of the Royal Dutch Academy of Sciences. (5)

Honors and Awards

 * 2020: Dutch National Research Agenda grant – “BioClock Consortium” (12)
 * 2016: Aschoff and Honma Prize in Biological Rhythm Research (14)
 * 1993: “Aschoff’s Rule, a prize for eminent contributions in Chronobiology supporting the interdisciplinary spirit of the field”. (13)
 * 1989: PhD, with honors. (5)
 * 1985: Doctoral exam, with honors. (5)