ABSTRACT
Background and Objectives: Physical function is influenced by light irradiation, and interest in the influence of light irradiation on health is high. Light signals are transmitted from the retina to the suprachiasmatic nucleus (SCN) via the retinal hypothalamic tract as non-image vision. Additionally, the SCN projects a nerve to the paraventricular nucleus (PVN) which acts as a stress center. This study examined the influences of three different light sources on neural activity in the PVN region using two different color temperatures. Materials and Methods: Experiments were conducted using twenty-eight Institute of Cancer Research (ICR) mice (10 week old males). Three light sources were used: (1) organic light-emitting diode (OLED) lighting, (2) LED lighting, and (3) fluorescent lighting. We examined the effects of light irradiation from the three light sources using two different color temperatures (2800 K and 4000 K). Perfusion was done 60 min after light irradiation, and then the brain was removed from the mouse for an immunohistochemistry analysis. c-Fos was immunohistochemically visualized as a marker of neural activity in the PVN region. Results: The number of c-Fos-positive cells was found to be significantly lower under OLED lighting and LED lighting conditions than under fluorescent lighting at a color temperature of 2800 K, and significantly lower under OLED lighting than LED lighting conditions at a color temperature of 4000 K. Conclusions: This study reveals that different light sources and color temperatures alter the neural activity of the PVN region. These results suggest that differences in the light source or color temperature may affect the stress response.
Subject(s)
Neurons/physiology , Paraventricular Hypothalamic Nucleus/physiopathology , Photic Stimulation/methods , Animals , Disease Models, Animal , Male , Mice , Paraventricular Hypothalamic Nucleus/abnormalities , Spectrophotometry/methodsABSTRACT
The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show here that Sim1 heterozygous mice are viable but develop early-onset obesity, with increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are hyperphagic but their energy expenditure is not decreased, distinguishing them from other mouse models of early-onset obesity such as deficiencies in leptin and melanocortin receptor 4. Quantitative histological comparison with normal littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer cells without a selective loss of any identifiable major cell type. Since acquired lesions in the PVN also induce increased appetite without a decrease in energy expenditure, we propose that abnormalities of PVN development cause the obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1. Pathways controlling the development of the PVN thus have the potential to cause obesity in both mice and humans.
Subject(s)
Hyperphagia/genetics , Obesity/genetics , Paraventricular Hypothalamic Nucleus/abnormalities , Repressor Proteins , Transcription Factors/physiology , Adipose Tissue/metabolism , Adipose Tissue/pathology , Adipose Tissue, Brown/cytology , Adipose Tissue, Brown/metabolism , Age Factors , Animals , Basic Helix-Loop-Helix Transcription Factors , Body Constitution/genetics , Female , Helix-Loop-Helix Motifs , Heterozygote , Insulin/blood , Male , Mice , Mice, Inbred Strains , Neurons/pathology , Sex Factors , Transcription Factors/geneticsABSTRACT
Insulin is a potent modulator of central nervous development and is suggested to influence the differentiation and maturation of hypothalamic structures involved in the regulation of body weight and metabolism. Hyperinsulinemic offspring of mothers with impaired glucose tolerance during pregnancy (gestational diabetes, GD) have an increased risk to develop overweight and diabetes mellitus during life, while the underlying pathophysiological mechanisms are still unknown. To investigate the effects of perinatal hyperinsulinism on the organization of hypothalamic regulators of body weight and metabolism, GD was induced in rats by application of streptozotocin on the day of conception (25 mg/kg, i.p.). On the 21st day of life, offspring of GD rats were overweight (p < 0.05) and hyperinsulinemic (p < 0.01). Using computer-assisted morphometric measurements, significantly decreased mean areas of neuronal nuclei and neuronal cytoplasm within the paraventricular hypothalamic nucleus (PVN; p < 0.01) and the ventromedial hypothalamic nucleus (VMN; p < 0.05) were observed in GD offspring. Analysis of topographically distinct parts revealed that these alterations particularly occurred in the parvocellular part of the PVN, as well as in the anterior, central, and dorsomedial part of the VMN. No morphometric alterations were found within the lateral hypothalamic area and the dorsomedial hypothalamic nucleus. In the arcuate hypothalamic nucleus, the mean area of neuronal cytoplasm was decreased (p < 0.05), while the number of neurons expressing tyrosine hydroxylase was clearly elevated (p < 0.002). For astrocytes, a tendency towards an increased glia/neuron ratio was observed in the periventricular hypothalamic area. These observations suggest disturbed differentiation and organization of distinct hypothalamic nuclei and subnuclei, respectively, in hyperinsulinemic offspring of GD rats, possibly leading to dysfunctions of hypothalamic regulators of body weight and metabolism which might contribute to the lifelong increased risk to develop overweight and diabetogenic disturbances.
