Circadian functioning of Locus Cœruleus of the nocturnal rat and diurnal rodent Arvicanthis.

The noradrenergic Locus Cœruleus is one of the major arousal structures involved in inducing wakefulness. While brain noradrenaline (NA) amounts display 24-h variations, the origin of NA rhythm is currently unknown. In this study, we tested the hypothesis that NA rhythm could result from its rhythmic synthesis.

Modelling herd immunity requirements in Queensland: impact of vaccination effectiveness, hesitancy and variants of SARS-CoV-2.

Long-term control of SARS-CoV-2 outbreaks depends on the widespread coverage of effective vaccines. In Australia, two-dose vaccination coverage of above 90% of the adult population was achieved. However, between August 2020 and August 2021, hesitancy fluctuated dramatically.

Bimodal serotonin synthesis in the diurnal rodent, Arvicanthis ansorgei.

In mammals, behavioral activity is regulated both by the circadian system, orchestrated by the suprachiasmatic nucleus (SCN), and by arousal structures, including the serotonergic system. While the SCN is active at the same astronomical time in diurnal and nocturnal species, little data are available concerning the serotonergic (5HT) system in diurnal mammals. In this study, we investigated the functioning of the 5HT system, which is involved both in regulating the sleep/wake cycle and in synchronizing the SCN, in a diurnal rodent, Arvicanthis ansorgei.

Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model.

Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis.

Observations in THY-Tau22 mice that resemble behavioral and psychological signs and symptoms of dementia.

THY-Tau22 mice constitute an animal model for tau aggregation, a hallmark in Alzheimer's disease (AD) and Tauopathies. Our previous studies have shown learning and memory deficits and changes in synaptic plasticity in the hippocampus in THY-Tau22 mice that are consistent with the learning impairments seen in AD-patients. However, behavioral disturbances are the most important problems in the management of AD and are major determinants of nursing home placement.

Glucocorticoid-mediated nycthemeral and photoperiodic regulation of tph2 expression.

In the Syrian hamster dorsal and median raphé nuclei, the tryptophan hydroxylase 2 gene (tph2), which codes the rate-limiting enzyme of serotonin synthesis, displays daily variations in its expression in animals entrained to a long but not to a short photoperiod. The present study aimed to assess the role of glucocorticoids in the nycthemeral and photoperiodic regulation of daily tph2 expression. In hamsters held in long photoperiod from birth, after adrenalectomy and glucocorticoid implants the suppression of glucocorticoid rhythms induced an abolition of the daily variations in tph2-mRNA concentrations, a decrease in the amplitude of body temperature rhythms and an increase in testosterone levels.

Complex regional influence of photoperiod on the nycthemeral functioning of the dorsal and median raphé serotoninergic system in the Syrian hamster.

The Syrian hamster (Mesocricetus auratus) is a widely used species for the study of biological clock synchronization and photoperiodism. The serotoninergic system arising from the median (MnR) and the dorsal raphé (DR) is a major actor in circadian clock synchronization. This serotoninergic system is also associated with functions and behaviours influenced by seasonal changes.

Local corticosterone infusion enhances nocturnal pineal melatonin production in vivo.

Melatonin, an important marker of the endogenous rhythmicity in mammals, also plays a role in the body defence against pathogens and injuries. In vitro experiments have shown that either pro- or anti-inflammatory agents, acting directly in the organ, are able to change noradrenaline-induced pineal indoleamine production. Whereas corticosterone potentiates melatonin production, incubation of the gland with tumour necrosis factor-alpha decreases pineal hormonal production.

Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity.

Tryptophan hydroxylase (TPH, the rate-limiting enzyme of serotonin synthesis) protein and mRNA levels display a circadian expression in the rat dorsal and median raphe. These patterns suggest a rhythmic synthesis of serotonin under the control of the master clock of suprachiasmatic nuclei. In the present study, we examined the involvement of endocrine and behavioral output signals of the master clock upon the Tph2 mRNA levels by quantitative in situ hybridization.

The serotonergic inhibition of slowly bursting cells in the intergeniculate leaflet of the rat.

Electrophysiological studies combined with local neurotoxic lesions were conducted on anaesthetized rats in order to determine whether the dorsal raphe nucleus (DRN) inhibits the intergeniculate leaflet (IGL) of the lateral geniculate nucleus by means of innervation by serotonin-containing fibres. In the control animals, electrical stimulation of the DRN induced the long-latency and long-lasting inhibition of the neuronal firing of the IGL cells that are characterized by rhythmic, slow-bursting activity in light conditions. The electrical destruction of the DRN resulted in an increase in the firing rate of the recorded IGL cells, whilst at the same time not affecting the rhythmic, bursting pattern of the activity.

Tissue-specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles.

Serotonin (5-HT) is involved in both photic and non-photic synchronization of the mammalian biological clock located in the suprachiasmatic nuclei (SCN). We have previously demonstrated that tryptophan hydroxylase protein (TPH), the rate-limiting enzyme of 5-HT synthesis, shows circadian rhythmicity in the pathways projecting from the raphe nuclei to the intergeniculate leaflets of the thalamus on one hand, and to the SCN on the other hand. In this study, we investigate whether the circadian rhythmicity in TPH protein could result from the rhythmic expression of tph gene in the raphe nuclei.

Circadian change in tryptophan hydroxylase protein levels within the rat intergeniculate leaflets and raphe nuclei.

Serotonin (5-HT) is involved in the synchronisation of the mammalian circadian clock located in the suprachiasmatic nuclei of the hypothalamus (SCN). This clock is synchronised by light (photic cues) and by non-photic cues. Non-photic cues are notably conveyed to the SCN by a direct 5-HT pathway arising from the mesencephalic median raphe nucleus (MRN).

Circadian tryptophan hydroxylase levels and serotonin release in the suprachiasmatic nucleus of the rat.

Serotonin (5-HT) plays an important role in the regulation of the time-keeping system in rodents. In the present study, we have investigated the interplay between the rhythms of 5-HT synthesis and release in the suprachiasmatic nuclei (SCN) of the rat. The quantitative distribution of tryptophan hydroxylase (TpH) protein was used as an index of 5-HT synthesis, in perikarya and terminals areas.

Ca increase in secretory granules of stimulated mast cells.

The elemental content of rat peritoneal mast-cell secretory granules has been measured by X-ray micro-analysis. Two distinct categories of granules were analyzed: intact granules, seen in control samples, and spumous granules, corresponding to exocytosed granule matrices. The average Ca content of intact granules was found to be approximately equal to cytosolic concentration, and to increase up to 40-fold in spumous granules.

Plasticity of tyrosine hydroxylase gene expression within BALB/C and C57Black/6 mouse locus coeruleus.

The plasticity of tyrosine hydroxylase (TH) phenotype in the locus coeruleus (LC) of two pure inbred strains of mice, Balb/C (C) and C57Black/6 (B6), was investigated at the molecular level by radioactive in situ hybridization. The results demonstrated that in basal conditions, C mouse LC contains less TH-mRNA-expressing cells than B6. After RU 24722-treatment, which induces long lasting TH gene expression in the LC, we previously reported an increase in TH-expressing cell number in C mouse LC only, equalizing TH phenotype between the two strains.

p-Chlorophenylalanine-induced alteration of somatodendritic levels of tryptophan hydroxylase within the rat mesencephalic raphe nuclei.

Tryptophan hydroxylase distribution was examined across the nuclei raphe dorsalis, medianus, and pontis of the adult rat, under basal conditions and 2 days after a single injection of p-chlorophenylalanine, an irreversible tryptophan hydroxylase inhibitor. Tryptophan hydroxylase-expressing cells were numbered in transverse sections processed for immunohistochemistry, and the area of tryptophan hydroxylase distribution was delineated in adjacent sections transferred onto nitrocellulose and processed for immunoautoradiography. Two distinct areas were visualized: an inner zone, corresponding to the area displaying tryptophan hydroxylase-immunoreactive cells (so-called somatic area), and an outer zone, here called perisomatic, devoid of perikarya yet rich in tryptophan hydroxylase-positive neuropil in the histological sections.

Ipsilateral alterations in tryptophan hydroxylase activity in rat brain after hypothalamic 5,7-di-hydroxytryptamine lesion.

The in vivo relationship between the amounts of tryptophan hydroxylase (TPH) protein and its intrinsic synthetic activity, measured by quantifying the amounts of alpha-[3H]methyl-5-hydroxytryptamine (alpha-[3H]M5-HT), is reported in cell body and terminal areas of intact and disturbed serotonergic neurons following a unilateral 5,7-dihydroxytryptamine (5,7-DHT) lesion of the dorsolateral hypothalamus. Five days after the lesion, the relationships between TPH and its synthetic product 5-HT were evaluated on adjacent brain sections in serotonergic cells bodies of the dorsal raphe nucleus (DRN) and nerve fibres of the medial forebrain bundle (MFB). On the side contralateral to the lesion, TPH and alpha-[3H]M5-HT levels in the intact hemi-DRN exhibited a caudo-rostral distribution and were positively and significantly correlated (p < or = 0.

Changes in steady-state levels of tryptophan hydroxylase protein in adult rat brain after neonatal 6-hydroxydopamine lesion.

A recently developed technique of immunoautoradiography on nitrocellulose transfers of serial frozen sections was used to determine tryptophan hydroxylase concentration in selected areas of the adult rat brain following neonatal 6-hydroxydopamine destruction of nigrostriatal dopamine neurons. Particular attention was paid to the neostriatum, known to be serotonin-hyperinnervated under these conditions, and to the nucleus raphe dorsalis, containing the cell bodies of origin for these nerve terminals. The hippocampus was also investigated as a territory of structurally intact serotonin innervation arising primarily from the nucleus raphe medianus.