7Alpha-hydroxypregnenolone mediates melatonin action underlying diurnal locomotor rhythms.

Melatonin regulates diurnal changes in locomotor activity in vertebrates, but the molecular mechanism for this neurohormonal regulation of behavior is poorly understood. Here we show that 7alpha-hydroxypregnenolone, a previously undescribed avian neurosteroid, mediates melatonin action on diurnal locomotor rhythms in quail. In this study, we first identified 7alpha-hydroxypregnenolone and its stereoisomer 7beta-hydroxypregnenolone in quail brain. These neurosteroids have not been described previously in avian brain. We then demonstrated that 7alpha-hydroxypregnenolone acutely increased quail locomotor activity. To analyze the production of 7alpha-hydroxypregnenolone, cytochrome P450(7alpha), a steroidogenic enzyme of this neurosteroid, was also identified. Subsequently, we demonstrated diurnal changes in 7alpha-hydroxypregnenolone synthesis in quail. 7Alpha-Hydroxypregnenolone synthesis and locomotor activity in males were much higher than in females. This is the first demonstration in any vertebrate of a clear sex difference in neurosteroid synthesis. This sex difference in 7alpha-hydroxypregnenolone synthesis corresponded to the sex difference in locomotion. We show that only males exhibited marked diurnal changes in 7alpha-hydroxypregnenolone synthesis, and these changes occurred in parallel with changes in locomotor activity. Finally, we identified melatonin as a key component of the mechanism regulating 7alpha-hydroxypregnenolone synthesis. Increased synthesis of 7alpha-hydroxypregnenolone occurred in males in vivo after melatonin removal via pinealectomy and orbital enucleation (Px plus Ex). Conversely, decreased synthesis of this neurosteroid occurred after melatonin administration to Px plus Ex males. This study demonstrates that melatonin regulates synthesis of 7alpha-hydroxypregnenolone, a key factor for induction of locomotor activity, thus inducing diurnal locomotor changes in male birds. This is a previously undescribed role for melatonin.

Effects of pinealectomy and exogenous melatonin on immunohistochemical ghrelin staining of arcuate nucleus and serum ghrelin leves in the rat.

Although the main source of circulating ghrelin is the stomach, it is also present in physiologically relevant amounts in the hypothalamus. It is reported that pharmacological doses of melatonin decrease blood levels of ghrelin. Thus, melatonin (MT) may be a candidate for the regulation of ghrelin synthesis in the brain. This study was therefore undertaken to investigate possible effects of pinealectomy and exogenous melatonin on hypothalamic ghrelin amount. Serum ghrelin levels following pinealectomy and administration of melatonin were also sought. Adult male Sprague-Dawley rats were divided into four groups as sham-operated (SHAM), sham-operated with melatonin treatment (SHAM-MT), pinealectomised (PNX) and melatonin-treated PNX (PNX-MT) groups. Ghrelin staining in the hypothalamus was determined by immunohistochemistry. Hypothalamic ghrelin was not observed in PNX rats. Much higher staining was detected in SHAM-MT rats compared to SHAM group. Lack of effect of melatonin on hypothalamic ghrelin in PNX rats implicates that exogenous melatonin requires an intact pineal to exert its effects. Although there were remarkable changes in the immunohistochemical activity of ghrelin in the hypothalamic arcuate nucleus, neither pinealectomy nor exogenous melatonin significantly changed serum levels of ghrelin. We have demonstrated for the first time that the pineal gland may play a role in ghrelin amount in the hypothalamus.

An Unusual Dermoid Cyst of the Pineal Region: Case Report in a Child

Introduction The pineal gland is a common location for intracranial germ cells, but dermoids are not commonly observed in this area. In the present paper, we discuss the clinical and radiological features as well as the treatment and outcome of this cyst in a 6-year- old child with a pineal dermoid cyst. Case Presentation The patient presented with chronic headache 6 months before admission in 2018. On the first admission, an enhanced lesion with a small cyst was detected in brain imaging. Magnetic resonance imaging (MRI) of the brain at follow-up (2 months after the first presentation) showed enlargement of the cyst size with compression on the adjacent structures. Radical excision of the tumor was performed after the endoscopic biopsy due to pressure exerted on the adjacent structures. Conclusion Dermoid cyst should be considered as a differential diagnosis for enhanced lesions of the pineal region.

Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats.

Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic-pituitary-adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures.

Diurnal changes of tonic nociceptive responses in mice: evidence for a proalgesic role of melatonin.

Diurnal variations in tonic pain reactions have been described in mice tested in Spring, but the underlying mechanisms are still unknown. We tested the potential role of melatonin, a key hormone in the control of neuro-endocrine circadian rhythms. The experiments were performed in male CBA/J mice housed under controlled temperature, humidity, and light (12/12 dark/light cycle) conditions, during the Light (7-10a.m.) or Dark (7-10p.m.) phases of the diurnal cycle. In a first group of experiments, animals were either pretreated with i.p. saline (controls) or with the melatonin receptor antagonist, luzindole (30 mg/kg), before the s.c. injection of a dilute formalin solution into a hindpaw. In control animals, pain-related behavioral reactions (licking and flinching) were higher in the evening (Dark) than in the morning (Light), both during the first (0-10 min) and the second (11-55 min) phase of the response to s.c. formalin. In animals pre-treated with luzindole, no diurnal changes occurred, pain reactions in the Dark being similar to those of the Light Control group. In a second group of experiments, artificial pinealectomy, obtained by exposing animals to continuous light for 48 h, also reduced pain reactions in the evening to levels comparable to those in the morning. Receptor autoradiography showed lower binding availability at spinal cord level in mice sacrificed during the Dark, as expected from the circadian pattern of melatonin secretion. A further significant decrease of melatonin receptor binding was induced by noxious stimulation. These results suggest a proalgesic role of endogenous melatonin in tonic pain.

Macrophages/microglia as 'sensors' of injury in the pineal gland of rats following a non-penetrative blast.

The pineal gland of adult rats was examined immunohistochemically and electron microscopically following exposure of the animals to a single blast equivalent to 110 kg TNT explosive. The most dramatic feature in rats killed at 7, 14 and 21 days after the blast was the upsurge of a large number of macrophages/microglia intensely immunostained with OX-42, OX-18, OX-6 and ED1 antibodies. These antibodies recognise the complement type three (CR3) receptors, major histocompatibility complex class I and class II (MHC I and MHC II) antigens and monocyte/macrophage antigens. Cell counts in OX-42 immunostained sections showed a two-fold increase at these intervals but returned to normal values at 28 days. The immunolabelled cells appeared extremely hypertrophic after the blast when compared with those in normal rats. In the latter and in rats killed at 28 days after the blast, immunoreactive cells were sparsely distributed. Ultrastructural study confirmed a wider occurrence of perivascular macrophages/microglia after the blast and the cells were laden with massive amounts of phagosomes resembling degenerating pinealocyte processes. It is concluded that the seemingly quiescent macrophages/microglia present normally in pineal gland were activated by the external blast force. The induced changes including the increase in cell numbers and endocytosis, however, were reversible in longer surviving animals.

The pineal gland is not essential for circadian expression of rat period homologue (rper2) mRNA in the suprachiasmatic nucleus and peripheral tissues.

To investigate the functional involvement of the pineal gland in circadian expression of the rat period homolog gene (rPer2) in the suprachiasmatic nucleus (SCN) and peripheral tissues, we performed Northern blot analysis in tissues from pinealectomized rats. The ectomy did not have any significant effects on rPer2 mRNA expression patterns both in a daily light-dark condition and in a constant darkness. These results suggest that the rhythmic secretion of pineal melatonin is not essential for the circadian expression of clock genes in the SCN and other peripheral tissues of rats.

Meningioma of the Pineal Region ­ Differential Radiologic Aspects of Pineal Region Tumors Based on a Clinical Case

Pineal region tumors are uncommon among neoplasm of the central nervous system, with this region being the most heterogeneous in terms of histological types. Meningiomas are rarer still, but can be found at this site, with origins in either the velum interpositum or falcotentorial junction. Neuroimaging exams can distinguish malignant from benign lesions besides helping to define the origin of the lesion as the pineal parenchymal or surrounding structures. We report the case of a woman with a pineal region tumor in which differential diagnoses included meningioma and germinoma, with confirmation of the former based on radiological characteristics and histopathology. In addition, a brief review of differential diagnoses and approaches for cases of lesions in this region is provided.

Os tumores da região da pineal apresentam uma baixa frequência entre as neoplasias do sistema nervoso central, sendo esta região a mais heterogênea em termos de tipos histológicos possíveis. Meningiomas são lesões ainda mais raras, porém possíveis de advirem desta localização, sejam originados do velum interpositum ou da junção falcotentorial. Os exames de neuroimagem permitem distinguir lesões malignas de benignas além de auxiliar na definição entre origem do parênquima pineal ou de estruturas adjacentes. Apresentamos o caso de uma mulher adulta com uma neoplasia da região da pineal cujos diagnósticos diferenciais incluíram meningioma e germinoma, evidenciando-se pelas características radiológicas e resultados histopatológicos tratar-se do primeiro. Além disso, fazemos uma breve revisão a respeito dos diagnósticos diferencias e condutas frente a uma lesão desta região.

Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken.

Despite the importance of intervertebral disc (IVD) degeneration both in research and clinical practice, the underlying biological mechanism of this phenomenon remains obscure. The current study investigated the effects of neonatal pinealectomy on the development of IVD degeneration process in chicken. Thirty chicks (3 days of age) were divided into two equal groups: unoperated controls (Group X) and pinealectomized chicks (Group Y). Pinealectomies were performed at the age of 3 days. At the age of 8 weeks, magnetic resonance imaging examination of one animal in each experimental group was taken. At the end of the study, serum melatonin level was determined by using ELISA method and histopathological or biochemical examination of specimens from all subjects was done. The results of biochemical analyses were compared using Mann-Whitney U test, whereas The Chi-square test was adopted for the histological findings. In this study, the serum melatonin levels in Group Y were significantly lower than those in Group X (P < 0.001). Similarly, scoliosis was developed in 14 out of 15 (93%) in Group Y. Hydroxyproline content of IVD tissue was high in Group Y compared with the values in Group X, although there was no significant difference. Histologically, an appearance of normal IVD was observed in Group X, while the presence of a degenerated IVD was observed in Group Y. From the results of the current study, it is evident that surgical pinealectomy in new-hatched Hybro Broiler chicks has a significant effect on serum melatonin level as well as on the development of IVD degeneration and spinal malformation. In the light of these results from present animal study, melatonin may play a role in the development of IVD degeneration in human beings, but this suggestion need to be validated in the human setting.

Late hydrocephalus in a case of wandering bullet into the pineal region.

We report a patient in whom a bullet in the brain migrated into the pineal region causing hydrocephalus 3 months later. In patients undergoing surgical removal of intracerebral or intraventricular bullets, it is recommended to obtain an x-ray or CT scan on the day of operation. Late hydrocephalus may occur several months after migration of the bullet due to scar tissue.