Risk of sleep problems in a clinical sample of children who stutter.

PURPOSE: Previous studies have shown increased prevalence of sleep problems among people who stutter. However, there is a lack of knowledge about what these sleep problems may specifically be. METHOD: Fifty children who stutter (CWS) from 6;0 to 12;9 years of age and 50 age- and gender-matched controls participated in this study. Parents did not report coexisting conditions, excepting stuttering and/or sleep problems. Sleep problems were investigated using a standardized questionnaire answered by parents. The questionnaire shows cut-off scores to identify the risk of sleep problems as a whole and on each one of the six subscales (i.e., disorders of initiating and maintaining sleep; sleep breathing disorders; disorders of arousal; sleep-wake transition disorders; disorders of excessive somnolence; and sleep hyperhidrosis). Scores above the cut-off are suggestive of sleep problems. RESULTS: Twenty-one CWS scored higher than the cut-off on the sleep questionnaire compared to only two controls (p < 0.00001). Specifically, CWS scored higher than controls in disorders of initiating and maintaining sleep, sleep-wake transition disorders (especially jerking, sleep talking, and bruxism), and disorders of excessive somnolence (p < 0.0083, corrected for multiple comparisons). DISCUSSION: Compared to controls, CWS are at greater risk for sleep problems, which are not consequences of coexisting disorders. Present findings confirm and expand current knowledge about sleep problems in CWS. Directionality possibilities and clinical implications are discussed.

LPS-induced inflammation in rats during pregnancy reduces maternal melatonin and impairs neurochemistry and behavior of adult male offspring.

Inflammation during pregnancy can induce neurodevelopmental changes that affect the neurological health of offspring. Elevated levels of circulating inflammatory cytokines have been shown to decrease nocturnal melatonin synthesis by the pineal gland, potentially impacting fetal development. This study aimed to assess the effects of LPS-induced inflammation on melatonin concentrations in the plasma of pregnant female rats and explore resulting neurochemical and behavioral changes in their offspring. Our findings revealed that pregnant rats injected with LPS experienced decreased nocturnal melatonin levels in their plasma, with an increase in diurnal melatonin content. The offspring exhibited reduced performance in tests evaluating motor coordination and spatial memory compared to control subjects. Immunohistochemical analysis indicated a decline in calbindin immunoreactivity in Purkinje cells in the cerebellum. Additionally, the hippocampus displayed an increase in IBA-1 and calretinin expression, coupled with a reduction in parvalbumin expression in the offspring of the LPS group. Collectively, this study provides compelling evidence that an inflammatory state can lead to a reduction in melatonin synthesis in pregnant females, potentially impacting the neurodevelopment of offspring, including neuronal, glial, motor, and cognitive aspects. Subsequent studies will further elucidate the mechanisms underlying inflammation-induced maternal melatonin reduction and its impact on offspring neurodevelopment.

Language skills development in children with congenital Zika virus syndrome.

BACKGROUND: The characterization of the phenotype of children with congenital Zika virus syndrome (CZS) is an ongoing process, since many characteristics can only be described with the advancing age of children providing some insights into the long-term sequelae. AIMS: To describe emerging findings on the impact of CZS on language development in children with CZS in a 4-year longitudinal study. METHODS AND PROCEDURES: 39 boys and 44 girls with CZS were allocated into four groups according to age ranging from 12 to 36 months. Language development was assessed using the Early Language Milestone Scale. OUTCOMES AND RESULTS: Visual, expressive, and receptive auditory skills of patients were lower than expected for their age. Despite producing vowel sounds, they did not babble; despite present hearing, the majority of the children did not understand simple commands. In over 4 years of follow-up, there was no evolution in language parameters, with the children stagnating at the language skills corresponding to 3 months of age. CONCLUSIONS AND IMPLICATIONS: Most children with CZS are not able to produce vocalic sounds, but some may be able to communicate basic needs through alternative communication. WHAT THIS PAPER ADDS?: Some babies with CZS died prenatally, at birth, or in the first year of life due to associated complications such as respiratory infection, dysphagia, and epilepsy. However, the functionality of the future remains uncertain for surviving babies. This study adds information about the impact of Zika Virus on the central nervous system and, consequently, the severity and complexity of the CZS language. Over 4 years of follow-up, no evolution in language parameters was observed in children with CSZ. Children with CZS demonstrate severe neurodevelopmental impairment, stagnating in language skills at the age of 3 months. In the future, some of them may be able to communicate their basic needs through alternative communication.

Obstructive sleep apnea and orofacial myofunctional aspects in obesity.

PURPOSE: This study aimed to evaluate the quality of sleep, presence of obstructive sleep apnea (OSA), and its relationship with the presence of snoring, cephalometric characteristics, degree of collapse of the upper airways, and orofacial myofunctional profile in obese and overweight individuals. METHODS: All participants completed polysomnography, as well as sleep and snoring questionnaires. We further performed orofacial, otorhinolaryngological, and anthropometric evaluations on all participants. RESULTS: A total of 102 adults, comprising 29 obese, 21 overweight, and 52 eutrophic individuals of both sexes participated in this study. We observed a high prevalence of snoring in both obese and overweight (100%), and in 65% of eutrophic individuals. Among the obese subjects 58% had a severe degree of OSA, whereas 4% of eutrophic subjects presented a risk for OSA development. Sleep quality was related to body mass index (BMI) and cervical and abdominal circumference. All obese and overweight individuals presented with orofacial myofunctional alterations such as facial asymmetry, alteration of the maxilla-jaw relationship, inadequate tongue posture, changes in masticatory pattern and swallowing, and inadequate general orofacial myofunctional condition. Airway obstructions at the retropalatal and retrolingual levels > 75% were observed in at least 48% of the individuals. CONCLUSION: Obese and overweight individuals presented a higher risk for the development of OSA compared with eutrophic patients, and obese individuals presented a greater severity of OSA. The higher the BMI and greater the cervical and abdominal circumferences, the higher the prevalence of OSA, worse the quality of sleep, and more serious orofacial myofunctional characteristics in this population.

Sleep disturbances and behavior in Smith-Magenis syndrome.

BACKGROUND: The Smith-Magenis syndrome (SMS) shows a collection of neurodevelopmental problems including mild to moderate intellectual disability, change-related anxiety, impulsivity, speech delay, Attention-Deficit/Hyperactivity Disorder (ADH) and sleep disturbances. Sleep disorders, when present, have been treated in several populations with consecutive improvements in cognitive and behavioral aspects. AIMS: To better understand the existing relationships between sleep disturbances and behavioral problems in SMS syndrome this study describes the sleep and behavior problems in the SMS and explores the possible relation between both. METHODS AND PROCEDURES: 17 individuals with SMS (50% males; 11.2 ± 4.9 years old) and 12 individuals with typical development (50% male; 11.1 ± 4.4 years old) were investigated using the Sleep Disturbance Scale for Children and the Child Behavior Checklist. RESULTS: A high percentage (60%) of individuals with SMS have an indication of sleep disorders, being the most frequent disorders the sleep-wake transition disorders, and disorders of initiating and maintaining sleep with sleep latency higher than acceptable and total sleep time below acceptable. More than 94% of the SMS group presented clinical or borderline scores on the total behavioral problems scale. The most common behavioral problems were Externalizing Problems, Thought and Attention, ADH and Aggressive problems. There was a positive correlation between disorders of initiating and maintaining sleep, sleep-wake transition disorders, disorders of arousal, disorders of excessive somnolence and behavioral problems. CONCLUSIONS AND IMPLICATIONS: The worse the sleep disturbances investigated, the more severe the behavioral problems characteristics reinforcing the importance to address the sleep problems in the treatment of SMS individuals.

Melatonin receptors and Per1 expression in the inferior olivary nucleus of the Sapajus apella monkey.

Melatonin is a transducer of photic environmental information and participates in the synchronization of various physiological and behavioral phenomena. Melatonin can act directly in several areas of the central nervous system through its membrane receptors coupled to G protein, called MT1 and MT2 receptors. In some structures, such as the retina, hypothalamus and pars tuberalis, the expression of both melatonin receptors shows circadian variations. Melatonin can act in the synchronization of the clock proteins rhythm in these areas. Using the immunohistochemistry technique, we detected the immunoexpression of the melatonin receptors and clock genes clock protein Per1 in the inferior olivary nucleus (ION) of the Sapajus apella monkey at specific times of the light-dark phase. The mapping performed by immunohistochemistry showed expressive immunoreactivity (IR) Per1 with predominance during daytime. Both melatonin receptors were expressed in the ION without a day/night difference. The presence of both melatonin receptors and the Per1 protein in the inferior olivary nucleus can indicate a functional role not only in physiological, as in sleep, anxiety, and circadian rhythm, but also a chronobiotic role in motor control mechanisms.

Sleep quality, functional skills, and communication in preschool-aged children with autism spectrum disorder.

AIM: This study aimed to correlate sleep quality, the performance of functional skills (mobility, self-care, and social function), communication, independence, and severity of ASD in children with ASD. METHOD: 58 children between 3 and 5 years and 11 months old were investigated. The Childhood Autism Rating Scale was applied to determine the severity of autism; the Sleep Disturbance Scale for Children was used to investigate sleep quality, and the Pediatric Evaluation of Disability Inventory to investigate functional abilities and independence of the children. RESULTS: 68.9 % of the children showed indicative of sleep disorders. There was no correlation between the different sleep disorders and communication. Sleep disorders showed a negative correlation with functional performance and a positive correlation with ASD severity. INTERPRETATION: The current study offers an exploration between sleep and functional skills in children with ASD. These findings provide important clinical implications in the diagnosis and intervention process of children with ASD and also stimulate reflections on the importance in minimize the impact of sleep disorders and functional abilities on the quality of life of these individuals and their families.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances.

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r = -.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r = -.31, P < .05) and positively associated with TNF level (r = .42, P < .01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

Dysregulation of Circadian Rhythms in Autism Spectrum Disorders.

BACKGROUND: The alterations in neurological and neuroendocrine functions observed in the autism spectrum disorder (ASD) involves environmentally dependent dysregulation of neurodevelopment, in interaction with multiple coding gene defects. Disturbed sleep-wake patterns, as well as abnormal melatonin and glucocorticoid secretion, show the relevance of an underlying impairment of the circadian timing system to the behavioral phenotype of ASD. Thus, understanding the mechanisms involved in the circadian dysregulation in ASD could help to identify early biomarkers to improve the diagnosis and therapeutics as well as providing a significant impact on the lifelong prognosis. OBJECTIVE: In this review, we discuss the organization of the circadian timing system and explore the connection between neuroanatomic, molecular, and neuroendocrine responses of ASD and its clinical manifestations. Here we propose interconnections between circadian dysregulation, inflammatory baseline and behavioral changes in ASD. Taking into account, the high relevancy of melatonin in orchestrating both circadian timing and the maintenance of physiological immune quiescence, we raise the hypothesis that melatonin or analogs should be considered as a pharmacological approach to suppress inflammation and circadian misalignment in ASD patients. STRATEGY: This review provides a comprehensive update on the state-of-art of studies related to inflammatory states and ASD with a special focus on the relationship with melatonin and clock genes. The hypothesis raised above was analyzed according to the published data. CONCLUSION: Current evidence supports the existence of associations between ASD to circadian dysregulation, behavior problems, increased inflammatory levels of cytokines, sleep disorders, as well as reduced circadian neuroendocrine responses. Indeed, major effects may be related to a low melatonin rhythm. We propose that maintaining the proper rhythm of the circadian timing system may be helpful to improve the health and to cope with several behavioral changes observed in ASD subjects.

Day/night melatonin content in cerebral palsy.

Changes in the sleep-wake cycle are frequent and may impair quality of life in individuals with cerebral palsy (CP). To investigate if a lack of a day/night variation of melatonin content could be related with sleep disorders (SD), the SD were evaluated with a Sleep Questionnaire and the melatonin content using ELISA in 33 individuals with CP and 24 controls. The indicative of SD were present in 47% of CP group, and the most frequent was the indicative of sleep breathing disorder. The CP group showed higher diurnal and lower nocturnal melatonin content than controls. Individuals with CP that had indicative of SD showed lower nocturnal content of melatonin than those without SD. These results showed that the lack of the day/night variation of melatonin was related to SD in individuals with CP.

Correlation between sleep profile and behavior in individuals with specific learning disorder. / Correlação entre o perfil do sono e o comportamento em indivíduos com transtorno específico da aprendizagem.

PURPOSE: This study aimed to correlate sleep profile and behavior in individuals with Specific Learning Disorder (SLD). METHODS: The Sleep General Habits Questionnaire, Sleep Diary, and Sleep Disturbance Scale for Children (SDSC) were used in analysis of sleep, whereas the Child Behavior Checklist (CBCL) inventory was used in analysis of behavior. RESULTS: 65.5% of the individuals with SLD presented symptoms of sleep disorders, most frequently wakefulness-sleep transition and sleep disturbance total score, which showed values higher than acceptable. In addition, individuals with SLD presented higher sleep latency than those with typical development. Concerning behavior, 72.4% of the individuals with SLD presented clinical condition of behavior problems. In the control group, none of the participants showed symptoms of sleep or behavior problems. In the SLD group, correlation was observed between behavioral problems and sleep disturbance. CONCLUSION: Individuals with SLD showed high rates of sleep disturbance and behavioral problems. The worse the sleep disturbance, the worse the behavioral aspects in these individuals.

OBJETIVO: Correlacionar o sono e o comportamento em indivíduos com transtorno específico da aprendizagem. MÉTODO: Na análise do sono, foram utilizados o Questionário de Hábitos Gerais de Sono, o Diário de Sono e a Escala de Distúrbios do Sono em Crianças (EDSC) e, para análise do comportamento, foi utilizado o Child Behavior Checklist (CBCL). RESULTADOS: 65,5% dos indivíduos com transtorno específico de aprendizagem apresentaram indicativo de distúrbios de sono, sendo os mais frequentes os distúrbios de transição sono-vigília e escores totais para distúrbios de sono acima do aceitável. Além disso, os indivíduos com transtorno específico de aprendizagem apresentaram maior latência de sono que o respectivo grupo controle. Quanto ao comportamento, 72,4% dos indivíduos com transtorno específico de aprendizagem apresentaram quadro clínico de problemas comportamentais. No grupo controle, nenhum dos participantes apresentou indicativo de problemas de sono ou comportamento. No grupo transtorno específico de aprendizagem, os distúrbios de sono encontrados apresentaram correlação com os problemas comportamentais. CONCLUSÃO: Indivíduos com transtorno específico da aprendizagem apresentaram altos índices de distúrbios de sono e alterações comportamentais. Quanto piores os distúrbios de sono, piores foram os aspectos comportamentais dos indivíduos com transtorno específico da aprendizagem.

Circadian Clock Proteins and Melatonin Receptors in Neurons and Glia of the Sapajus apella Cerebellum.

Oscillations of brain proteins in circadian rhythms are important for determining several cellular and physiological processes in anticipation of daily and seasonal environmental rhythms. In addition to the suprachiasmatic nucleus, the primary central oscillator, the cerebellum shows oscillations in gene and protein expression. The variety of local circuit rhythms that the cerebellar cortex contains influences functions such as motivational processes, regulation of feeding, food anticipation, language, and working memory. The molecular basis of the cerebellar oscillator has been demonstrated by "clock gene" expression within cells of the cerebellar layers. Genetic and epidemiological evidence suggests that disruption of circadian rhythms in humans can lead to many pathological conditions. Despite this importance, data about clock gene and protein expression in the cerebellum of diurnal (day-active) species, specifically primates, is currently poorly explored, mainly in regard to cellular identity, as well as the relationship with other molecules also involved in cerebellar functions. These studies could contribute to clarification of the possible mechanisms behind cerebellar rhythmicity. Considering that calcium binding proteins (CaBPs) play crucial roles in preserving and modulating cerebellar functions and that clock gene expression can be controlled by afferent projections or paracrine circadian signals such as the hormone melatonin, the present study aimed to describe cellular identities, distribution patterns and day/night expression changes in PER1, PER2, CaBPs, and MT1 and MT2 melatonin receptors in the cerebellar cortex of a diurnal primate using conventional fluorescence and peroxidase-antiperoxidase immunocytochemical techniques. PER1 and PER2 immunoreactive (IR) cells were observed in the Purkinje cells of the cerebellum, and MT1 and MT2 receptors were localized around Purkinje cells in the Pj layer in Bergmann cells. This identity was confirmed by the S100ß-IR of these cells. The highest expression of PER seen in the daytime analysis coincided with the highest expression of melatonin receptors. CaBPs showed day/night morphological and density changes in the cerebellar cortex. The presence of the same temporal variations in the expression of PER in the Pj neurons and in MT1 and MT2 receptors in Bergmann cells indicates a possible relation between these cells during the rhythmic processing of the cerebellum, in addition to the CaBP temporal morphological and density changes.

Sleep findings in Brazilian children with congenital Zika syndrome.

Study Objectives: Zika virus infection during pregnancy may result in congenital Zika syndrome (CZS), whose characteristics are being described. Methods: The present study aimed to investigate the sleep characteristics of 136 infants/toddlers (88 with CZS and 48 with typical development (TD), age and gender matched, 60% girls and 40% boys in both groups) using the Brief Infant Sleep Questionnaire. The ages of children in both groups ranged from 5 to 24 months (CZS 15.9 ± 0.4 vs. TD 15.8 ± 1.0 months, P= 0.90). Results: The results show that 34.1% of CZS and 2% of TD children were defined as poor sleepers, 15% of CZS and 2% of TD children remained awake at night for a period longer than 1 hour, and 24% of CZS and 2% of TD children slept less than 9 hours. The CZS group showed shorter total sleep time (CZS 11.24 ± 2.6 vs. TD 12.02 ± 1.9 hours, P= 0.03) and shorter nocturnal sleep duration than the TD group (CZS 8.2 ± 0.2 vs. TD 9.4 ± 0.2 hours, P= 0.0002). In contrast to the control group (P= 0.02, r= -0.34), in the CZS group, no correlation was found between age and nocturnal wakefulness. Future studies should explore these data in relation to the development and maturation of the central nervous system of these children. Conclusions: Considering the well-known consequences of poor sleep quality on health in several populations, the presence of sleep disorders should be considered in CZS using multidisciplinary treatments.

Correlação entre o perfil do sono e o comportamento em indivíduos com transtorno específico da aprendizagem / Correlation between sleep profile and behavior in individuals with specific learning disorder

RESUMO Objetivo Correlacionar o sono e o comportamento em indivíduos com transtorno específico da aprendizagem. Método Na análise do sono, foram utilizados o Questionário de Hábitos Gerais de Sono, o Diário de Sono e a Escala de Distúrbios do Sono em Crianças (EDSC) e, para análise do comportamento, foi utilizado o Child Behavior Checklist (CBCL). Resultados 65,5% dos indivíduos com transtorno específico de aprendizagem apresentaram indicativo de distúrbios de sono, sendo os mais frequentes os distúrbios de transição sono-vigília e escores totais para distúrbios de sono acima do aceitável. Além disso, os indivíduos com transtorno específico de aprendizagem apresentaram maior latência de sono que o respectivo grupo controle. Quanto ao comportamento, 72,4% dos indivíduos com transtorno específico de aprendizagem apresentaram quadro clínico de problemas comportamentais. No grupo controle, nenhum dos participantes apresentou indicativo de problemas de sono ou comportamento. No grupo transtorno específico de aprendizagem, os distúrbios de sono encontrados apresentaram correlação com os problemas comportamentais. Conclusão Indivíduos com transtorno específico da aprendizagem apresentaram altos índices de distúrbios de sono e alterações comportamentais. Quanto piores os distúrbios de sono, piores foram os aspectos comportamentais dos indivíduos com transtorno específico da aprendizagem.

ABSTRACT Purpose This study aimed to correlate sleep profile and behavior in individuals with Specific Learning Disorder (SLD). Methods The Sleep General Habits Questionnaire, Sleep Diary, and Sleep Disturbance Scale for Children (SDSC) were used in analysis of sleep, whereas the Child Behavior Checklist (CBCL) inventory was used in analysis of behavior. Results 65.5% of the individuals with SLD presented symptoms of sleep disorders, most frequently wakefulness-sleep transition and sleep disturbance total score, which showed values higher than acceptable. In addition, individuals with SLD presented higher sleep latency than those with typical development. Concerning behavior, 72.4% of the individuals with SLD presented clinical condition of behavior problems. In the control group, none of the participants showed symptoms of sleep or behavior problems. In the SLD group, correlation was observed between behavioral problems and sleep disturbance. Conclusion Individuals with SLD showed high rates of sleep disturbance and behavioral problems. The worse the sleep disturbance, the worse the behavioral aspects in these individuals.

Daily corticosterone rhythm modulates pineal function through NFκB-related gene transcriptional program.

Melatonin and glucocorticoids are key hormones in determining daily rhythmicity and modulating defense responses. In nocturnal animals, corticosterone peaks at light/dark transition,while melatonin peaks at the middle of the night in both nocturnal and diurnal animals. The crosstalk between adrenal and pineal glands under inflammatory conditions indicates that corticosterone potentiates nocturnal melatonin synthesis by reducing the activity of NFκB. This transcription factor, which modulates the expression of a key enzyme in melatonin synthesis, is sharply reduced at the entrance of darkness in the rat pineal gland. In this study, we established the basis for understanding the crosstalk between adrenal and pineal glands in physiological conditions. Here we show that the expression of 70 out of 84 genes implied in defense responses exhibit a sharp reduction exactly at the entrance of darkness. Mifepristone impair the changes of 13 out of 84 genes, suggesting that the rhythm of corticosterone modulates pineal phenotype, as mifepristone also reduces the expression of Aanat and the nocturnal synthesis of melatonin. Therefore, darkness-induced synthesis of the pineal hormone, besides being controlled by the central clock located in the hypothalamus, is also influencedby glucocorticoids through the regulation of NFκB transcriptional program.

Melatonin and circadian rhythms in autism: Case report.

Among the most co-occurring conditions in autism spectrum disorders (ASD), there are sleep disorders which may exacerbate associated behavioral disorders and lead to intensification of existing autistic symptoms. Several studies investigating the use of melatonin in the treatment of sleep disorders in ASD have shown comparative efficiency in sleep with little or no side effects. Here we report a case of ASD with non-24-hour rhythm and the effect of melatonin in circadian parameters by actigraphy. Visual analysis of the first 10 days recorded and the periodogram suggest that this patient showed a non-24-hour rhythm. This ASD subject showed before melatonin administration an activity/rest rhythm lower than 24 hours. The results show that melatonin increased approximately 4.7 times the regularity of circadian activity rhythm and resting staying on average between 00:00 and 06:00 and showed positive effects in improving the quality of sleep and behavior. So, the actigraphy showed an ASD subject with a non-24-hour activity/rest rhythm which changed this rhythm to a 24-hour rhythm after melatonin administration. This result reinforces the prospect of therapy with melatonin for synchronization (increased regularity) of endogenous rhythms and improve sleep quality and hence behavior and indicates the actigraphy as a choice tool to characterize several parameters of the activity/rest rhythm of ASD individuals.

Day/night expression of MT1 and MT2 receptors in hypothalamic nuclei of the primate Sapajus apella.

Melatonin is involved in the temporal organization of several physiological and behavioral events, controlled by hypothalamic nuclei, like sleep, feeding, reproduction and metabolic modulation and acts through two types of high-affinity G protein-coupled membrane receptors: MT1 and MT2. This study aimed to investigate the expression of MT1 and MT2 receptors proteins in four hypothalamic nuclei, i.e., SCN, supraoptic (SON), paraventricular (PVN) and anteroventral periventricular nuclei (AVPV), of the diurnal primate Sapajus apella using immunohistochemistry. Since these areas are involved in the expression of biological rhythms, they are candidates to have variations in their neurochemistry, so the MT1 and MT2 expression has been analyzed at a point in light and another in the dark phase. Both receptors were found to have day/night differences in the four hypothalamic nuclei with an apparent inverse expression in the SCN compared with the other areas. These differences could be related to the idea that the individual should be prepared to respond by different ways to melatonin signal within the several processes and can contribute to the efficacy of melatonin ligands or melatonin in therapies.

Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation.

OBJECTIVE: The clock genes Period (per) 1 and 2 are essential components in the generation and adjustment of biological circadian rhythms by the suprachiasmatic nucleus (SCN). Both genes are also rhythmically present in extrahypothalamic areas such as the hippocampus and cerebellum, considered subordinate oscillators. Several pathological conditions alter rhythmic biological phenomena, but the mechanisms behind these changes involving the clock genes are not well defined. The current study investigated changes in PER1 and PER2 immunoreactivity in the SCN, hippocampus, and cerebellum in a neuroinflammation model. METHODS: Wistar rats received lipopolysaccharide (LPS) or vehicle intracerebroventricularly. The melatonin plasmatic content was quantified by ELISA to confirm the alterations in biological rhythms, and PER1 and PER2 immunoreactivities were analyzed in brain sections by immunohistochemistry. RESULTS: In the SCN, intracerebroventricular LPS changed PER1 expression, increasing the number of PER1-immunoreactive (IR) cells at zeitgeber time (ZT) 15, decreasing it at ZT5 and ZT20 and not changing it at ZT10. LPS also induced a decrease in PER2-IR cells at ZT5, ZT10, and ZT15 but not at ZT20 in the SCN. In the hippocampus, LPS induced a decrease in PER1-IR and PER2-IR cells at both ZTs (ZT10 and ZT15). In the cerebellum, LPS increased the number of PER1-IR cells at ZT10 and decreased it at ZT15, while the number of PER2-IR cells was reduced at both ZTs. CONCLUSIONS: These results indicate that a neuroinflammatory condition leads to desynchronization of primary and subordinate brain oscillators, supporting the existence of the integration between the immune and the circadian system.

Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats.

Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM) is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC), such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60) was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals) by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

Oropharyngeal swallowing in chronic renal failure.

OBJECTIVE: To characterize the oropharyngeal swallowing profile of patients with chronic renal failure. METHODS: A cross-sectional clinical study involving 20 adults diagnosed with chronic renal failure in hospital stay was conducted. The evaluation of swallowing was performed by videofluoroscopy, and characterization of findings was based on effectiveness and safety parameters. Functional Oral Intake Scale (FOIS) was also applied. RESULTS: On videofluoroscopy, 16 patients presented changes in oral and pharyngeal patterns, three individuals presented impairment at the pharyngeal phase, and only one individual presented changes only at the oral phase of swallowing. Furthermore, videofluoroscopy showed penetration and tracheal aspiration in 30% of the sample. Before the videofluoroscopy, four individuals (20%) were at level 5 of FOIS scale, whereas 16 individuals (80%) were at level 7. After adjustments of the oral diet consistency because of safety and swallowing effectiveness, FOIS classification was six individuals at level 1, seven at level 4, four at level 5, and three at level 6. CONCLUSION: The characterization of oropharyngeal swallowing profile in chronic renal patients showed abnormalities at oral and pharyngeal phase, including penetration and tracheal aspiration, which requires oral intake changes.