RESUMEN
Repetitive mild traumatic brain injury (RmTBI) is a prevalent and costly head injury particularly among adolescents. These injuries may result in long-term consequences, especially during this critical period of development. Insomnia and sleeping difficulties are frequently reported following RmTBI and greatly impair recovery. We sought to develop an animal model of exacerbated deficits following RmTBI by disrupting the hypothalamic circadian system. To accomplish this, we conducted RmTBI on adolescent rats that had received neonatal injections of monosodium glutamate (MSG), a known hypothalamic neurotoxin. We then examined behavioral, circadian, and epigenetic changes. MSG treated rats showed lower anxiety-like behaviors and displayed poor short-term working memory. We also showed changes in the morphology of the circadian clock in the suprachiasmatic nucleus (SCN) vasoactive intestinal polypeptide (VIP) immunostaining. VIP optical density in the SCN increased with MSG but decreased with RmTBI. There were changes in the expression of the clock genes and upregulation of the orexin receptors in response to RmTBI. MSG treated rats had longer telomere lengths than controls. Finally, although both MSG and RmTBI alone produced attenuated circadian amplitudes of activity and body temperature, exacerbated deficits were not identified in animals that received MSG and RmTBI. In sum, both MSG and RmTBI can alter behavior, circadian rhythm amplitude, SCN morphology, and gene expression independently, but the effects do not appear to be additive. Specific damage in the hypothalamus and SCN should be considered when patients experience sleeping problems following RmTBI, as this may improve therapeutic strategies.
Asunto(s)
Conmoción Encefálica/metabolismo , Hipotálamo/metabolismo , Animales , Ansiedad/metabolismo , Ansiedad/patología , Temperatura Corporal , Conmoción Encefálica/patología , Ritmo Circadiano/fisiología , Femenino , Expresión Génica , Hipotálamo/crecimiento & desarrollo , Hipotálamo/patología , Masculino , Memoria a Corto Plazo/fisiología , Actividad Motora/fisiología , Distribución Aleatoria , Ratas Sprague-Dawley , Recurrencia , Glutamato de Sodio/efectos adversos , Núcleo Supraquiasmático/crecimiento & desarrollo , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/patología , TelómeroRESUMEN
The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.
Asunto(s)
Cistinil Aminopeptidasa/metabolismo , Hipotálamo/enzimología , Hipotálamo/patología , Neuronas/enzimología , Neurohipófisis/metabolismo , Esquizofrenia/patología , Anciano , Autopsia , Enfermedad Crónica , Femenino , Glutamato-Amoníaco Ligasa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Neurofisinas/metabolismo , Oxitocina/metabolismo , Núcleo Hipotalámico Paraventricular/patología , Núcleo Supraquiasmático/patología , Vasopresinas/metabolismoRESUMEN
Despite advances in promoting axonal regeneration after adult central nervous system injury, elicitation of a large number of lesion-passing axons reform active synaptic connections with natural target neurons remains limited. By deleting both Pten and Socs3 in retinal ganglion cells, we report that optic nerve axons after prechiasm lesion robustly reinnervate the hypothalamus, form new synapses with neurons in the suprachiasmatic nucleus (SCN), and re-integrate with the existing circuitry. Photic or electric stimulation of the retinal axons induces neuronal response in SCN. However both the innervation pattern and evoked responses are not completely restored by the regenerating axons, suggesting that combining with other strategies is necessary to overcome the defective rewiring. Our results support that boosting the intrinsic growth capacity in injured neurons promotes axonal reinnervation and rewiring.
Asunto(s)
Axones/fisiología , Hipotálamo/fisiología , Regeneración Nerviosa/fisiología , Nervio Óptico/fisiología , Fosfohidrolasa PTEN , Células Ganglionares de la Retina/fisiología , Proteínas Supresoras de la Señalización de Citocinas , Núcleo Supraquiasmático/fisiología , Sinapsis/fisiología , Animales , Axones/patología , Hipotálamo/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Nervio Óptico/patología , Fosfohidrolasa PTEN/genética , Células Ganglionares de la Retina/patología , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/genética , Núcleo Supraquiasmático/patología , Sinapsis/patologíaRESUMEN
The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does not influence the BOLD response to ghrelin.
Asunto(s)
Encéfalo/patología , Regulación de la Expresión Génica , Ghrelina/metabolismo , Homeostasis , Imagen por Resonancia Magnética , Animales , Encéfalo/metabolismo , Estradiol/metabolismo , Conducta Alimentaria , Femenino , Hipotálamo/metabolismo , Hipotálamo/patología , Sistema Límbico/fisiología , Masculino , Núcleo Accumbens/patología , Núcleo Hipotalámico Paraventricular/patología , Corteza Prefrontal/patología , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/metabolismo , Recompensa , Transducción de Señal , Núcleo Supraquiasmático/patología , Factores de TiempoRESUMEN
Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Cronoterapia , Ritmo Circadiano/fisiología , Fototerapia , Enfermedad de Alzheimer/terapia , Animales , Relojes Circadianos/fisiología , Humanos , Ratones , Núcleo Supraquiasmático/patologíaRESUMEN
Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes associated with these disorders. Thus, there appears to be a strong association between the circadian system and mood regulation, although the mechanisms that underlie this association are unclear. Recently, a number of studies in animal models have begun to shed light on the complex interactions between circadian genes and mood-related neurotransmitter systems, the effects of light manipulation on brain circuitry, the impact of chronic stress on rhythms, and the ways in which antidepressant and mood-stabilizing drugs alter the clock. This review will focus on the recent advances that have been gleaned from the use of pre-clinical models to further our understanding of how the circadian system regulates mood.
Asunto(s)
Afecto/fisiología , Ritmo Circadiano/fisiología , Trastornos del Humor/fisiopatología , Afecto/efectos de los fármacos , Animales , Ritmo Circadiano/efectos de los fármacos , Cricetinae , Evaluación Preclínica de Medicamentos , Humanos , Ratones , Modelos Animales , Trastornos del Humor/tratamiento farmacológico , Trastornos del Humor/epidemiología , Ratas , Estrés Psicológico/fisiopatología , Estrés Psicológico/psicología , Núcleo Supraquiasmático/patología , Núcleo Supraquiasmático/fisiología , Núcleo Supraquiasmático/fisiopatologíaRESUMEN
The pineal hormone melatonin is involved in the regulation of circadian rhythms and feeds back to the central biological clock, the hypothalamic suprachiasmatic nucleus (SCN) via melatonin receptors. Supplementary melatonin is considered to be a potential treatment for aging and Alzheimer's disease (AD)-related circadian disorders. Here we investigated by immunocytochemistry the alterations of the MT1 melatonin receptor, the neuropeptides vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the SCN during aging and AD. We found that the number and density of AVP/VIP-expressing neurons in the SCN did not change, but the number and density of MT1-expressing neurons in the SCN were decreased in aged controls compared to young controls. Furthermore, both MT1-expressing neurons and AVP/VIP-expressing neurons were strongly diminished in the last neuropathological stages of AD (Braak stages V-VI), but not in the earliest stages (Braak stages I-II), compared to aged controls (Braak stage 0). Our study suggests that the MT1-mediated effects of melatonin on the SCN are disturbed during aging and even more so in late stage AD, which may contribute to the clinical circadian disorders and to the efficacy of therapeutic melatonin administration under these conditions.
Asunto(s)
Envejecimiento/metabolismo , Enfermedad de Alzheimer/patología , Regulación de la Expresión Génica/fisiología , Receptor de Melatonina MT1/metabolismo , Núcleo Supraquiasmático/metabolismo , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Cambios Post Mortem , Receptor de Melatonina MT1/genética , Estadísticas no Paramétricas , Núcleo Supraquiasmático/patología , Péptido Intestinal Vasoactivo/genética , Péptido Intestinal Vasoactivo/metabolismo , Vasopresinas/genética , Vasopresinas/metabolismoRESUMEN
OBJECTIVE: Preliminary data suggest that morning bright light might improve symptoms of agitation, a serious problem in patients with dementia. The authors expand on an earlier pilot study by evaluating the effect of bright light therapy on agitated behavior in a large sample of patients with severe dementia. METHODS: Ninety-two patients were randomly assigned to morning bright light, morning dim red light, or evening bright light. Agitation was rated by research staff who observed the patients every 15 minutes throughout the treatment period and by caregivers at one time-point before and one time-point after treatment. RESULTS: Morning bright light delayed the acrophase of the agitation rhythm by over 1.5 hours. Bright light was associated with improved caregivers' ratings but had little effect on observational ratings of agitation. CONCLUSION: Although the result that light shifted the peak of the agitated behavior might be generalizable to patients with milder forms of AD, the fact that agitation was not ameliorated might not be. Because the suprachiasmatic nucleus (SCN) of patients with severe AD is likely to be more degenerated, and the circadian activity rhythms deteriorate as the disease progresses, it is still possible that patients with more intact SCNs, that is, patients with mild or moderate AD, might benefit from light treatment even more than those with severe AD.
Asunto(s)
Enfermedad de Alzheimer/rehabilitación , Institucionalización , Fototerapia , Agitación Psicomotora/terapia , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Atrofia/patología , Ritmo Circadiano/fisiología , Trastornos del Conocimiento/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Casas de Salud , Agitación Psicomotora/complicaciones , Agitación Psicomotora/diagnóstico , Índice de Severidad de la Enfermedad , Núcleo Supraquiasmático/patologíaRESUMEN
The cellular expression of nitric oxide synthase (NOS) was studied in neurons of the Nuc. suprachiasmaticus (SCN) of depressed patients and matched controls. The number of NOS-immunoreactive SCN neurons was significantly reduced in depression. We conclude that affective disorders are accompanied by impaired hypothalamic NO signaling.
Asunto(s)
Trastorno Depresivo/fisiopatología , Hipotálamo/enzimología , Óxido Nítrico Sintasa/genética , Óxido Nítrico/fisiología , Transducción de Señal/fisiología , Núcleo Supraquiasmático/enzimología , Trastorno Depresivo/genética , Trastorno Depresivo/patología , Regulación Enzimológica de la Expresión Génica , Humanos , Hipotálamo/patología , Inmunohistoquímica , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa de Tipo I , Valores de Referencia , Núcleo Supraquiasmático/patologíaRESUMEN
Circadian rhythm disturbances are frequently present in Alzheimer disease (AD). In the present study, we investigated the expression of vasopressin (AVP) mRNA in the human suprachiasmatic nucleus (SCN). The in situ hybridization procedure on formalin-fixed paraffin-embedded material was improved to such a degree that we could, for the first time, visualize AVP mRNA expressing neurons in the human SCN and carry out quantitative measurements. The total amount of AVP mRNA expressed as masked silver grains in the SCN was 3 times lower in AD patients (n = 14; 2,135 +/- 597 microm2) than in age- and time-of-death-matched controls (n = 11; 6,667 +/- 1466 microm2) (p = 0.003). No significant difference was found in the amount of AVP mRNA between AD patients with depression (n = 7) and without depression (n = 7) (2,985 +/-1103 microm2 and 1,285 +/- 298 microm2, respectively; p = 0.38). In addition, the human SCN AVP mRNA expressing neurons showed a marked day-night difference in controls under 80 years of age. The amount of AVP mRNA was more than 3 times higher during the daytime (9,028 +/- 1709 microm2, n = 7) than at night (2,536 +/- 740 microm2, n = 4; p = 0.02), whereas no clear diurnal rhythm of AVP mRNA in the SCN was observed in AD patients. There was no relationship between the amount of AVP mRNA in the SCN and age at onset of dementia, duration of AD and the neuropathological changes in the cerebral cortex. These findings suggest that the neurobiological basis of the circadian rhythm disturbances that are responsible for behavioral rhythm disorders is located in the SCN. It also explains the beneficial effects of light therapy on nightly restlessness in AD patients.
Asunto(s)
Enfermedad de Alzheimer/genética , Arginina Vasopresina/genética , Ritmo Circadiano/genética , Depresión/complicaciones , Expresión Génica , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Envejecimiento/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Arginina Vasopresina/deficiencia , Arginina Vasopresina/metabolismo , Ritmo Circadiano/fisiología , Femenino , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Índice de Severidad de la Enfermedad , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/patologíaRESUMEN
The present study was aimed at characterizing the effects of low-protein malnutrition (6% casein) on the circadian rhythm of drinking behavior and on suprachiasmatic nuclei immunohistochemistry in Sprague-Dawley rats. Recordings were started at 30 days of age under a 12:12-h light-dark (LD) cycle. At age 150 days, recordings were continued under constant dim red light, and finally the latency to entrain to complete and skeleton photoperiods was established. At the end of the recordings rats were processed for histological analysis. Compared with their controls, malnournished rats exhibited 1) splitting of rhythmicity under LD that 2) condensed to one component in constant dim red light, 3) delayed entrainment to skeleton photoperiod, and 4) precocious entrainment under complete photoperiod. Immunohistochemical analysis showed mainly a decrease in the immunohistochemical detection of vasoactive intestinal polypeptide and glial fibrillar acid protein cells in malnourished animals. These results indicate that in malnourished rats there is a decrease 1) in the coupling force among the oscillators and 2) in the strength of the phase lock between the oscillators and the light-dark cycle.
Asunto(s)
Ritmo Circadiano/fisiología , Trastornos Nutricionales/fisiopatología , Núcleo Supraquiasmático/fisiopatología , Animales , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipotálamo/metabolismo , Inmunohistoquímica , Masculino , Trastornos Nutricionales/metabolismo , Trastornos Nutricionales/patología , Fotoperiodo , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Núcleo Supraquiasmático/patología , Péptido Intestinal Vasoactivo/metabolismoAsunto(s)
Enfermedad de Alzheimer/fisiopatología , Ritmo Circadiano/fisiología , Enfermedades Hipotalámicas/fisiopatología , Trastorno de la Conducta Social/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Arginina Vasopresina/fisiología , Mapeo Encefálico , Femenino , Humanos , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/patología , Hipotálamo/patología , Hipotálamo/fisiopatología , Masculino , Persona de Mediana Edad , Fases del Sueño/fisiología , Trastorno de la Conducta Social/diagnóstico , Trastorno de la Conducta Social/patología , Núcleo Supraquiasmático/patología , Núcleo Supraquiasmático/fisiopatología , Péptido Intestinal Vasoactivo/fisiología , Vigilia/fisiologíaRESUMEN
In the Royal College of Surgeons (RCS) rat, characterized by inherited retinal dystrophy, retinal projections to the brain were studied using anterograde neuronal transport of cholera toxin B subunit upon injection into one eye. The respective immunoreactivity was found predominantly contralateral to the injection site in the lateral geniculate nucleus, superior colliculus, nucleus of the optic tract, medial terminal nucleus of the accessory optic tract, and bilateral hypothalamic suprachiasmatic nuclei. Although terminal density was somewhat reduced in dystrophic rats, the projection patterns in these animals appeared similar to those seen in their congenic controls and were comparable to the visual pathways described for the rat previously. In dystrophic rats, the number of cell bodies exhibiting immunoreactivity to vasoactive intestinal polypeptide, viz. a population of suprachiasmatic neurons receiving major retinohypothalamic input, was reduced by one-third, and some differences were observed in the termination pattern of the geniculohypothalamic tract, as revealed by immunoreactivity to neuropeptide Y in the suprachiasmatic nucleus.
Asunto(s)
Vías Aferentes/patología , Hipotálamo/patología , Retina/patología , Degeneración Retiniana/patología , Núcleo Supraquiasmático/patología , Vías Aferentes/metabolismo , Animales , Toxina del Cólera/inmunología , Toxina del Cólera/farmacología , Femenino , Cuerpos Geniculados/metabolismo , Hipotálamo/inmunología , Masculino , Neuropéptido Y/metabolismo , Ratas , Ratas Endogámicas , Retina/metabolismo , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
Following inoculation of the KOS strain of herpes simplex virus type 1 (HSV-1) into one anterior chamber of euthymic BALB/c mice, virus spreads from the injected eye to the central nervous system and from the central nervous system to the optic nerve and retina of only the uninoculated eye. In contrast, in athymic BALB/c mice or mice depleted of both CD4+ and CD8+ T cells, virus spreads to the optic nerve and retina of both the injected eye and the uninjected eye. To determine the location in the central nervous system where spread of virus to the optic nerve and retina of the injected eye is prevented, euthymic BALB/c mice were injected with a mixture of KOS and RH116, a mutant of KOS that contains the Escherichia coli beta-galactosidase (beta-gal) gene. Several animals were sacrificed each day; serial frozen sections of the brain were prepared and sequential sections were stained for beta-gal or for T cells. At all sites except the suprachiasmatic nuclei, virus and T cells arrived at approximately the same time. However, at day 5 post inoculation (PI), T cells were present in both the ipsilateral and the contralateral suprachiasmatic nuclei, but only the ipsilateral suprachiasmatic nucleus was virus-positive. Since virus spreads from the ipsilateral suprachiasmatic nucleus to the contralateral optic nerve, these results suggest that T cells infiltrating the area of the contralateral suprachiasmatic nucleus prior to the arrival of virus at this site prevent virus spread into the optic nerve of the inoculated eye.
Asunto(s)
Encéfalo/inmunología , Herpes Simple/inmunología , Herpesvirus Humano 1 , Nervio Oculomotor/inmunología , Linfocitos T/patología , Animales , Encéfalo/patología , Encéfalo/virología , Femenino , Herpes Simple/patología , Herpesvirus Humano 1/aislamiento & purificación , Hipotálamo/inmunología , Hipotálamo/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos/inmunología , Nervio Oculomotor/patología , Núcleo Supraquiasmático/inmunología , Núcleo Supraquiasmático/patología , Linfocitos T/inmunología , Linfocitos T/virología , Factores de Tiempo , beta-Galactosidasa/análisisRESUMEN
The expression of locomotor activity by golden hamsters is temporally controlled by circadian oscillators contained within the suprachiasmatic nucleus (SCN). A genetic mutation has been found that alters the freerunning period of the locomotor activity rhythm from the wild-type value of approximately 24 hours to approximately 20 hours in homozygous mutants. It has been shown previously that a transplant of fetal hypothalamic tissue containing the SCN to a host rendered arrhythmic by a complete lesion of the SCN restores rhythmicity with the freerunning period which is normally expressed by the donor genotype. To investigate the mechanisms by which the SCN controls the temporal organization of behavior, we made partial lesions to the SCN of hosts of one genotype, and then placed hypothalamic implants from fetal donors of a different genotype into the lesion site. By varying the size of the host's partial SCN lesion and the duration of time between lesioning and transplantation, we have attempted to alter the relative amount of host and donor control over the expression of locomotor activity. We found that the expression of donor rhythmicity requires the presence of a lesion to the host SCN, and that the incidence of donor expression increased as a function of host SCN lesion size. Neither the duration of time between lesioning and transplantation, nor the location of the transplant within the third ventricle had independent effects on the incidence of donor rhythm expression; however, there was a strong suggestion of an effect of their interaction.
Asunto(s)
Trasplante de Tejido Encefálico , Ritmo Circadiano/fisiología , Trasplante de Tejido Fetal , Hipotálamo/fisiología , Núcleo Supraquiasmático/fisiología , Animales , Conducta Animal/fisiología , Cricetinae , Hipotálamo/patología , Mesocricetus , Actividad Motora/fisiología , Núcleo Supraquiasmático/patologíaRESUMEN
In a previous study we described abnormalities in cytoarchitecture and vasoactive intestinal polypeptide distribution in the suprachiasmatic nucleus (SCN) of anophthalmic mice. However, the effect of anophthalmia on the geniculohypothalamic pathway, an important pathway for relay of photic information to the SCN, is not known. The present study examined the geniculohypothalamic pathway in congenitally anophthalmic and sighted control mice. The data demonstrate that the development of an intergeniculate leaflet (IGL), the expression of neuropeptide Y (NPY) by IGL neurons and the formation of NPY terminal fields in the SCN proceed in the absence of retinal input. Although the cytoarchitectural organization of the anophthalmic IGL differs from that of the control mouse, the distribution of NPY plexuses in the suprachiasmatic nucleus is remarkably similar.
Asunto(s)
Anoftalmos/patología , Cuerpos Geniculados/patología , Hipotálamo/patología , Animales , Benzoxazinas , Histocitoquímica , Ratones , Ratones Endogámicos , Vías Nerviosas/patología , Neuropéptido Y/metabolismo , Oxazinas , Retina/fisiología , Núcleo Supraquiasmático/patologíaRESUMEN
Differences in sleep-wake patterns in response to light-dark stimulation have been observed between albino Lewis and pigmented Brown Norway strains of rats, which may be associated with albinism. Since several anatomical differences have been demonstrated in the visual pathways of albino and pigmented mammals, the present study was undertaken to determine whether additional differences in visual pathways of these rat strains exist that might account for their behavioral differences. Using anterograde tracing techniques and image analysis, we have investigated the retinal projections of Lewis and Brown Norway rats. Our results demonstrate that the distribution of retinal terminals in the hypothalamic suprachiasmatic nucleus extends over a greater area in Lewis compared to Brown Norway rats. This zone of termination corresponds to a cytoarchitectonically definable ventrolateral subdivision of the suprachiasmatic nucleus (SCN), which is also greater in Lewis than in Brown Norway rats. These results may have implications for behaviors related to the SCN.
Asunto(s)
Albinismo/patología , Hipotálamo/patología , Pigmentación , Ratas Endogámicas Lew/anatomía & histología , Ratas/anatomía & histología , Retina/patología , Animales , Retina/fisiopatología , Núcleo Supraquiasmático/patología , Transmisión Sináptica , Vías Visuales/patologíaRESUMEN
Vibratome sectioning of paraformaldehyde-fixed brains containing a lesion and/or intracerebroventricular grafts and staining of these sections often lead to damage around the site of the lesion and loss of the implants. Various embedding procedures were compared in order to find a method to overcome this problem. The best results were obtained when fixed brain tissue was first embedded under reduced pressure in 10% gelatin at 50 degrees C, and then fixed again, in 4% paraformaldehyde. The method did not affect the immunocytochemical staining for vasopressin, vasoactive intestinal polypeptide, somatostatin, gonadotropin releasing hormone and neuropeptide Y.
Asunto(s)
Ventrículos Cerebrales/patología , Hipotálamo/patología , Adhesión del Tejido/métodos , Animales , Trasplante de Tejido Encefálico/fisiología , Gelatina , Inmunohistoquímica , Microtomía , Ratas , Ratas Endogámicas , Núcleo Supraquiasmático/patología , Fijación del TejidoRESUMEN
Morphometric analysis of the human hypothalamus revealed that the volume of the suprachiasmatic nucleus (SCN) in homosexual men is 1.7 times as large as that of a reference group of male subjects and contains 2.1 times as many cells. In another hypothalamic nucleus which is located in the immediate vicinity of the SCN, the sexually dimorphic nucleus (SDN), no such differences in either volume or cell number were found. The SDN data indicate the selectivity of the enlarged SCN in homosexual men, but do not support the hypothesis that homosexual men have a 'female hypothalamus'.