RESUMEN
Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic-related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay. We found that chronic stress decreased the expression of three sympathetic markers in the pineal gland, tyrosine hydroxylase, the p75 neurotrophin receptor and alpha-tubulin, while the same treatment did not affect the expression of the non-specific sympathetic markers Erk1 and Erk2, and glyceraldehyde-3-phosphate dehydrogenase. Furthermore, these results were correlated with a significant increase in plasma melatonin concentration in stressed rats when compared with control animals. Our findings indicate that stress may impair pineal sympathetic inputs, leading to an abnormal melatonin release that may contribute to environmental maladaptation. In addition, we propose that the pineal gland is a target of glucocorticoid damage during stress.
Asunto(s)
Melatonina/sangre , Glándula Pineal/metabolismo , Estrés Psicológico/sangre , Sistema Nervioso Simpático/metabolismo , Animales , Biomarcadores/metabolismo , Enfermedad Crónica , Regulación hacia Abajo/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Gliceraldehído 3-Fosfato/metabolismo , Inmunohistoquímica , Masculino , Melatonina/metabolismo , Actividad Motora/fisiología , Glándula Pineal/inervación , Ratas , Ratas Sprague-Dawley , Receptor de Factor de Crecimiento Nervioso/metabolismo , Restricción Física , Estrés Psicológico/fisiopatología , Fibras Simpáticas Posganglionares/metabolismo , Fibras Simpáticas Posganglionares/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Tubulina (Proteína)/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Regulación hacia Arriba/fisiologíaRESUMEN
The pineal gland is innervated by postganglionic sympathetic nerves from the superior cervical ganglion. As theaxons enter the gland, they synapse with the pinealocytes. In this report, we describe a case in which the conarii nervewas observed crossing the distal portion of the ascending branch of the venous sinus, thus penetrating the capsule ofthe pineal gland. The nerve observed consisted of a bundle of unmyelinated axons and collagen fibers which aresurrounded by endothelial cells. This is the first report of a completely engulfed and detached conarii nerve within avenous sinus.
Asunto(s)
Animales , Masculino , Glándulas Endocrinas , Fibras Nerviosas/fisiología , Glándula Pineal/fisiología , Glándula Pineal/inervación , Glándula Pineal , Aves/anatomía & histología , Diagnóstico por Imagen , Glutaral , Microscopía Electrónica , FosfatosRESUMEN
ATP is coreleased with noradrenaline in several noradrenergic synapses, and P2-like receptors were shown to be present in rat pineal glands. A new method of functional investigation was developed to assess the importance of both transmitters (noradrenaline and ATP) in eliciting the synthesis of melatonin and its precursor N'-acetyl-5-hydroxytryptamine (N'-acetyl-5-HT) through transmural electrical field stimulation of cultured pineal glands. Incubation with the beta-adrenoceptor antagonist propranolol (>10(-7) M) blocked almost completely the production of N'-acetyl-5-HT, whilst the P2 receptor antagonists pyridoxalphosphate-6 azophenyl-2',4'-disulfonic acid (PPADS, >3x10(-6) M) and suramin (>10(-6) M) blocked it partially. These findings indicate a physiologically relevant role for the purinergic cotransmission in this system.
Asunto(s)
Adenosina Trifosfato/metabolismo , Norepinefrina/metabolismo , Glándula Pineal/metabolismo , Fosfato de Piridoxal/análogos & derivados , Serotonina/análogos & derivados , Transmisión Sináptica/fisiología , Antagonistas Adrenérgicos beta/farmacología , Animales , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Femenino , Técnicas In Vitro , Masculino , Melatonina/metabolismo , Glándula Pineal/efectos de los fármacos , Glándula Pineal/inervación , Propranolol/farmacología , Fosfato de Piridoxal/farmacología , Ratas , Ratas Wistar , Serotonina/metabolismo , Suramina/farmacología , Factores de TiempoRESUMEN
In man, the rate of resting salivary secretion can be influenced by environmental stimuli related to light dark cycles or by noxious stimuli (stressors) of psychological origin. The sympathetic branch of the autonomic nervous system and the adrenal medulla play an important part in homeostatic responses. Previous observations have shown that chronic exposure of rats to constant light promotes degranulation of parotid acini and desensitization of submandibular beta-adrenergic receptors. Now the submandibular secretory response elicited by beta- and alpha2-adrenergic agonists was studied in rats chronically exposed to environmental conditions that modified the activities of sympathetic efferents to the pineal, salivary and adrenal glands. Adult male rats were exposed to constant light (LL) or constant darkness (DD) for 20 days, or to stress (2 h daily immobilization) for 14 days. Control animals were kept under the usual lighting conditions and without immobilization. Dose response curves to isoproterenol (i.v), before and after administration (i.v.) of a dose (20 microg/kg) of clonidine were obtained. Beta-adrenergic desensitization was observed in all the experimental groups, while alpha2-adrenergic desensitization was only observed in the stress and LL groups. The results suggest that circulating catecholamines could mediate light and stress effects on submandibular beta-adrenergic secretory responses. Extrasynaptic alpha2-adrenoceptors might modulate the submandibular secretory response when predictable environmental stimuli (daily light phase) or unpredictable stressors raise the concentrations of circulating catecholamines.
Asunto(s)
Ambiente , Receptores Adrenérgicos alfa 2/fisiología , Receptores Adrenérgicos beta/fisiología , Estrés Fisiológico/fisiopatología , Glándula Submandibular/fisiología , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/inervación , Glándulas Suprarrenales/fisiología , Agonistas alfa-Adrenérgicos/administración & dosificación , Agonistas alfa-Adrenérgicos/sangre , Agonistas alfa-Adrenérgicos/farmacología , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/farmacología , Animales , Ritmo Circadiano , Clonidina/administración & dosificación , Clonidina/farmacología , Oscuridad , Relación Dosis-Respuesta a Droga , Vías Eferentes/efectos de los fármacos , Vías Eferentes/fisiología , Inmovilización , Inyecciones Intravenosas , Isoproterenol/administración & dosificación , Isoproterenol/farmacología , Iluminación , Masculino , Norepinefrina/sangre , Glándula Pineal/efectos de los fármacos , Glándula Pineal/inervación , Glándula Pineal/fisiología , Ratas , Ratas Wistar , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Receptores Adrenérgicos beta/efectos de los fármacos , Saliva/metabolismo , Glándula Submandibular/efectos de los fármacos , Glándula Submandibular/inervación , Glándula Submandibular/metabolismo , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiologíaRESUMEN
Since gonadal denervation and pineal deafferentation by cervical superior ganglionectomy affect sexual development, this study was performed to evaluate testicular steroidogenesis, spermatogenesis and the cervical superior ganglion (CSG) histology in rats treated with guanethidine (GD). The treatment was performed by GD s.c. injections for 3 weeks, from the 21st day of age to the 41st day of age (pre-puberty), when the animals were sacrificed. Different doses were used: group A = 10 mg/kg/day, group B = 50 mg/kg/day and saline (control group). Testicular denervation was confirmed by HPLC for catecholamines in testicular tissue. Testicular concentrations (TC) of progesterone (P4) and testosterone (T) were measured by RIA. Significantly higher TC of P4 and lower TC of T were observed only in group A in comparison with group B and the control group. No alteration of sperm production was observed in either treated group. Histological analysis of CSG showed only few neuronal alterations in group A rats, while in group B the nervous cells were practically destroyed. This suggests that 10 mg/kg/day GD treatment probably produces a specific blockade of 17 alpha-hydroxylase/17,20 desmolase at pre-puberty leading to a decrease of the androgen production. However, in the 50 mg/kg/day group no differences were observed concerning the steroid profiles, this result being attributed to the extensive damage to the CSG observed only in group B. The CSG destruction causes deafferentation of the pineal gland producing abolishment of the inhibition of the 17 alpha-hydroxylase/17,20 desmolase promoted by melatonin or by an out of phase production of androgen.
Asunto(s)
Glándula Pineal/inervación , Glándula Pineal/fisiología , Testículo/crecimiento & desarrollo , Testículo/inervación , Animales , Ganglionectomía , Guanetidina/administración & dosificación , Masculino , Progesterona/biosíntesis , Ratas , Ratas Wistar , Maduración Sexual/efectos de los fármacos , Maduración Sexual/fisiología , Espermatogénesis/fisiología , Esteroide 17-alfa-Hidroxilasa/metabolismo , Ganglio Cervical Superior/efectos de los fármacos , Ganglio Cervical Superior/patología , Ganglio Cervical Superior/fisiopatología , Simpatectomía Química , Testículo/fisiología , Testosterona/biosíntesisRESUMEN
Since ovary denervation causes delayed puberty, we investigated the relative importance of ovary innervation on the morphology and physiology of theca interstitial cells (TIC) and granulosa cells (GC) in female rats at pre-puberty. Elimination of the sympathetic innervation was performed by long term post natal treatment with guanethidine (GD), an adrenergic blocking agent. The sympathectomized rats exhibited: reductions in follicular volume (40%), granulosa cells area (43%) and theca interstitial cell volume (50%). Ovarian concentrations of pregnenolone (P5) and progesterone (P4) were decreased whereas no differences were observed in androstenedione (A) and estradiol (E2). The intensity of the immunocytochemical reaction for 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) detected only in interstitial cells, did not show any difference. These in vivo results include the TIC in the bulk of ovarian structures affected by GD denervation at pre-puberty as it was already observed for GC. The reduced area/volume occupied by these cells in the GD treated ovary is associated to a blockade of the initial steps of the steroidogenic pathway, probably at the level of the cholesterol side chain cleavage enzyme (P450 s.c.c.), previously to P5 synthesis, since P5 is reduced. Similar intra ovarian concentrations of androgens are discussed in terms of possible pineal deafferentation promoted by GD at high doses.
Asunto(s)
Células de la Granulosa/citología , Células de la Granulosa/fisiología , Ovario/inervación , Células Tecales/citología , Células Tecales/fisiología , Antagonistas Adrenérgicos , Androstenodiona/metabolismo , Animales , Estradiol/metabolismo , Femenino , Guanetidina , Inmunohistoquímica , Ovario/citología , Ovario/fisiología , Glándula Pineal/inervación , Glándula Pineal/fisiología , Pregnenolona/metabolismo , Progesterona/metabolismo , Ratas , Ratas Wistar , Maduración Sexual/fisiología , Simpatectomía QuímicaRESUMEN
1. The pineal gland is regulated primarily by photoperiodic information attaining the organ through a multisynaptic pathway initiated in the retina and the retinohypothalamic tract. 2. Norepinephrine (NE) released from superior cervical ganglion (SCG) neurons that provide sympathetic innervation to the pineal acts through alpha1- and beta 1- adrenoceptors to stimulate melatonin synthesis and release. 3. The increase in cyclic AMP mediated by beta 1-adrenergic activation is potentiated by the increase in Ca2+ flux, inositol phospholipid turnover, and prostaglandin and leukotriene synthesis produced by alpha 1-adrenergic activation. 4. Central pinealopetal connections may also participate in pineal control mechanisms; transmitters and modulators in these pathways include several neuropeptides, amino acids such as gamma-aminobutyric acid (GABA) and glutamate, and biogenic amines such as serotonin, acetylcholine, and dopamine. 5. Secondary regulatory signals for pineal secretory activity are several hormones that act on receptors sites on pineal cells or at any stage of the neuronal pinealopetal pathway.