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PubMed2006

Sensory neuronal phenotype in galanin receptor 2 knockout mice: focus on dorsal root ganglion neurone development and pain behaviour.

Galanin is a 29-amino-acid peptide expressed in dorsal root ganglion (DRG) neurones and spinal dorsal horn neurones. It affects pain threshold and has developmental and trophic effects. Galanin acts at three G-protein-coupled receptors, galanin receptors (GalR1-3), each expressed in the DRGs as suggested by in situ hybridization and/or reverse transcriptase-polymerase chain reaction. The GalR2 knockout (-/-) mice permit studies on the contributions of this receptor subtype to the role of galanin at the spinal level. At 1 week after sciatic nerve transection (axotomy), there were 16-20% fewer neurones in intact and contralateral DRGs of -/- mice as compared with wild-type (WT) mice. In addition, a significant neurone loss (26% reduction) was found in the ipsilateral DRGs of WT mice, whereas no further neurone loss was seen in -/- mice. Expression of several peptides has been examined after axotomy, including galanin, neuropeptide Y and two of its receptors as well as substance P, and no significant differences were found between -/- and WT mice in either ipsi- or contralateral DRGs, respectively. After thermal injury and spinal nerve ligation, onset and duration of hyperalgesia in the injured paw were similar in GalR2-/- and WT animals. Recovery from spinal nerve ligation-caused allodynia had the same kinetics in -/- and WT animals. These data are in line with earlier observations from the peripheral and central nervous system, suggesting that galanin actions mediated by GalR2 subtype are of importance in neurodevelopment and neuroprotection.

Age Factors↗

PubMed2006

The development of emotional face processing during childhood.

Our facial expressions give others the opportunity to access our feelings, and constitute an important nonverbal tool for communication. Many recent studies have investigated emotional perception in adults, and our knowledge of neural processes involved in emotions is increasingly precise. Young children also use faces to express their internal states and perceive emotions in others, but little is known about the neurodevelopment of expression recognition. The goal of the current study was to determine the normal development of facial emotion perception. We recorded ERPs in 82 children 4 to 15 years of age during an implicit processing task with emotional faces. Task and stimuli were the same as those used and validated in an adult study; we focused on the components that showed sensitivity to emotions in adults (P1, N170 and frontal slow wave). An effect of the emotion expressed by faces was seen on the P1 in the youngest children. With increasing age this effect disappeared while an emotional sensitivity emerged on N170. Early emotional processing in young children differed from that observed in the adolescents, who approached adults. In contrast, the later frontal slow wave, although showing typical age effects, was more positive for neutral and happy faces across age groups. Thus, despite the precocious utilization of facial emotions, the neural processing involved in the perception of emotional faces develops in a staggered fashion throughout childhood, with the adult pattern appearing only late in adolescence.

Adolescent↗

PubMed2006

Infant motor development is associated with adult cognitive categorisation in a longitudinal birth cohort study.

BACKGROUND: The relationship between the age of reaching infant developmental milestones and later intellectual function within the normal population remains unresolved. We hypothesised that the age of learning to stand in infancy would be associated with adult executive function and that the association would be apparent throughout the range of abilities, rather than confined to extremes. METHODS: The Northern Finland 1966 Birth Cohort is based upon 12,058 live-born children in a geographic and temporally defined population. Information on age at learning to stand without support was obtained at one year. At age 33-35 a random sample of 104 subjects underwent a neuropsychological test battery including tests of executive function (cognitive categorisation), visuo-spatial memory, verbal learning and visual object learning. We investigated associations between developmental data and adult neuropsychological test scores. RESULTS: There was a significant linear relationship between age of learning to stand and adult categorisation: the earlier the attainment of the milestone, the better was the categorisation. No such relationships were observed between infant neurodevelopment and adult cognition in other neuropsychological domains. CONCLUSION: Even within the normal range of development, early development in the gross motor domain is associated with better adult executive function (in tests of categorisation). Investigation of the determinants and sequelae of normal neural development will facilitate research into a variety of neurodevelopmental disorders.

Adult↗

PubMed1988

Epilepsy precipitated by bathing.

A case of epilepsy precipitated by bathing is described and previously reported cases are reviewed. The prognosis for this rare form of reflex epilepsy seems to be good, in that the seizures resolve with age and neurodevelopment remains normal.

Baths↗

PubMed1994

Relation between neurodevelopmental status of very preterm infants at one and eight years.

The relation between neurodevelopmental status at one and eight years of age was investigated in a cohort of 207 infants born between 1979 and 1982 at < 33 weeks of gestation. The probability of a major disabling impairment at eight years was only 1 per cent among 164 children with normal neurodevelopment at one year, but 56 per cent for the 43 impaired children and 92 per cent for the 23 of these who had major disabling impairments. Close correspondence was found between the type of major impairment diagnosed at one and eight years. Neurodevelopmental status at one year also predicted the need for extra educational provision by eight years, with probabilities of 9 per cent for children without impairment at one year, 56 per cent for impaired children and 87 per cent for those with major impairments. Similarly, neurodevelopmental status predicted an IQ of more than 2 SD below the mean (< 70), with probabilities of 0, 30 per cent and 48 per cent, respectively.

Child↗

PubMed1998

Visual, cognitive, and neurodevelopmental outcome at 51/2 years in children with perinatal haemorrhagic-ischaemic brain lesions.

To determine predictive values of early visual and neurocognitive assessment in children with perinatally acquired haemorrhagic or ischaemic brain lesions selected on the basis of ultrasound, 63 children (37 boys, 26 girls), who had been followed and examined until the age of 18 months, were reexamined at 5 1/2 years. Good correlations between visual and neurodevelopmental assessments at 18 months and at 5 1/2 years were found. When ultrasound abnormalities were combined with early visual and neurocognitive assessment data, good predictive values, especially for the group of children who had grade 2 to 4 leukomalacia, were found for visual acuity and neurodevelopment.

Brain↗

PubMed1992

Long term predictive value of Doppler studies in high risk fetuses.

OBJECTIVE: To determine whether the predictive value of Doppler ultrasonography extends beyond the perinatal period. DESIGN: Descriptive follow-up study. SETTING: Specially designated paediatric clinic in Royal Maternity Hospital. SUBJECTS: 40 children who as high risk fetuses had had assessment of umbilical artery flow velocity waveforms. INTERVENTIONS: Parental history, physical examination, anthropometry, Denver developmental screening test. OUTCOME MEASURES: Weight, height, head circumference, neurological impairment, Denver development screening test RESULT: Abnormal waveforms were an accurate predictor of neonatal outcome, with significant differences in birthweight, gestational age, need for nursery admission, and frequency of intrauterine growth retardation between normal and abnormal waveform groups. However, abnormal Doppler studies were not predictive of long-term adverse sequelae. There were no significant differences in height, head circumference, proportion with neurological impairment, or results of Denver developmental screening test at a median age of five years. CONCLUSION: The predictive value of Doppler ultrasonography is less for long-term growth and neurodevelopment than for perinatal outcome in the high risk fetus.

Child↗

PubMed2001

Outcome for children born after in utero laser ablation therapy for severe twin-to-twin transfusion syndrome.

OBJECTIVE: To examine the postnatal development of a group of children born after in utero laser ablation therapy for severe twin-to-twin transfusion syndrome. DESIGN: Retrospective cohort outcome study involving assessment of neurodevelopment and physical well being. SETTING: Harris Birthright Centre, King's College Hospital, London. PARTICIPANTS: Twins and singleton survivors treated via laser ablation therapy for twin-to-twin transfusion syndrome over a four-year period. METHODS: Of 54 families contacted to participate in the study, who had been treated for twin-to-twin transfusion syndrome during a four-year period, 24 families attended for paediatric assessment; 12 pairs of twins and 12 singleton survivors were assessed for perinatal, neurological and neurodevelopmental outcome using the Griffiths scales of mental development. A further 20 families were assessed via a proforma after contact with their general practitioner. A comparison of these groups showed no significant differences in sociodemographic factors or severity of disease between responders (44 families, 81.5%) and non-responders (10 families). RESULTS: The group of children assessed by a paediatrician had low birthweight (1619g donor, 1814g recipient, 1877g singleton) and had been born preterm (33 weeks twins, 31.2 weeks singleton) with attendant increased resuscitation, neonatal unit admission (mean 40 days) and instrumental delivery. Mean Griffiths scores were within the normal range of ability (91.2 donor vs 97.7 recipient and 101.6 singletons) with the only significant difference being in the locomotor subscale where donor (82.6) and recipient (85.3) were less than singletons: -99.1 (P < 0.05). There was no cerebral palsy in the singleton survivors, but there were five cases in the twin group. All except one affected child (with quadriplegia) had mean Griffiths scores in the normal range. In the GP proforma group there was one case, in a twin, of cerebral palsy. CONCLUSION: The overall cerebral palsy rate was 9%: 0% in the singleton survivors group and 13.3% in the twin survivors group. This pilot data highlights the need for careful long term follow up of children affected by twin-to-twin transfusion syndrome.

Child, Preschool↗

PubMed2005

Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability.

Although the roles of cyclin-dependent kinase 5 (Cdk5) in neurodevelopment and neurodegeneration have been studied extensively, regulation of Cdk5 activity has remained largely unexplored. We report here that glutamate, acting via NMDA or kainate receptors, can induce a transient Ca(2+)/calmodulin-dependent activation of Cdk5 that results in enhanced autophosphorylation and proteasome-dependent degradation of a Cdk5 activator p35, and thus ultimately down-regulation of Cdk5 activity. The relevance of this regulation to synaptic plasticity was examined in hippocampal slices using theta burst stimulation. p35(-/-) mice exhibited a lower threshold for induction of long-term potentiation. Thus excitatory glutamatergic neurotransmission regulates Cdk5 activity through p35 degradation, and this pathway may contribute to plasticity.

Animals↗

PubMed2005

Demographic characteristics and clinical course in infants with moderate or severe neonatal encephalopathy.

A chart review of 64 infants with moderate or severe neonatal encephalopathy showed that resuscitation was required for 61 (95%), respiratory support for 53 (83%) and anticonvulsants for 58 (91%). Death occurred in 2 (4%) infants with moderate encephalopathy and 12 (86%) with severe encephalopathy. In addition, subsequent neurodevelopment was abnormal in approximately a quarter of infants who survived after a moderate to severe encephalopathy.

Brain Diseases↗

PubMed2006

Imaging cerebral activity in recovery from chronic traumatic brain injury: a preliminary report.

People in chronic phase of traumatic brain injury (TBI) are often told that there will be no further recovery in brain function, that they are in a "static phase." Holistic Approach to NeuroDevelopment and Learning Efficiency (HANDLE), an alternative therapy, aims to improve function by teaching a series of physical and mental activities that clients perform and encouraging changes in lifestyle. Five subjects (3 males) with chronic TBI (at least 3 years since ictus) completed the HANDLE Institute's program and were prospectively evaluated. Each had six regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) scans over 7 months (scans n= 30). Paired scans were performed with injection of Tc-99m ECD to image rCBF at rest and during the HANDLE "Crossed Arm Bounce" (CAB) exercise before the program, at 3-4 months into the program, and at 6-7 months, after the program had ended. SPECT images were analyzed statistically using Neurostat in which image sets were coregistered and warped into Talaraich atlas for pairwise subtraction between conditions. Group analysis of SPECT showed that CAB activated (increased rCBF) vermis and cerebellar hemispheres in first two paired scans and anterior cingulate and vermis on the final pair. Increased rCBF at rest occurred in cerebellar hemispheres, vermis, and right dorsomedial frontal cortex. These preliminary observations suggest that there may be a role of the hindbrain (vermis and cerebellum) with HANDLE treatment of chronic TBI.

Adult↗

PubMedDate not supplied

Outcomes for children exposed to drugs in utero.

Substance abuse among pregnant women remains a national health issue. The incidence of infants born addicted to licit and illicit substances is increasing. The long-term outcomes have not been consistently documented. These appear to include mild to severe developmental and cognitive problems, depending upon the substance used. Central nervous system problems, behavioral dysfunction, and safety issues are major parental concerns for these children as they grow. Interventions must be aimed at thorough assessments, including an accurate maternal history, use of supports for positive neurodevelopment, parent education about infant/child cues, and encouragement of educational environments that are highly structured and safe. Consistent, long-term follow-up is essential to optimize long-term outcomes.

Child Abuse↗

PubMed1998

Seasonality of birth in epilepsy: a Danish study.

OBJECTIVES: A recent British epidemiological study, having found that the seasonality of birth in a large epileptic sample was significantly different from that of the general population, has pointed to neurodevelopmental disruption as the likely mechanism to cause at least part of the epilepsies of unknown aetiology. The aim of this study is to replicate the British study using a large Danish sample. MATERIAL AND METHODS: The population studied is composed by all the 50,886 patients discharged from Danish Hospitals, with a diagnosis of epilepsy, in the period from 1977 to 1993. The seasonal pattern of birth in this sample has been compared, using regression methods, with all the live births in Denmark. RESULTS: The results were strikingly similar to the British study, with a deficit of epileptic births in September and an excess during the winter months. CONCLUSION: This study seems to confirm the seasonal presence in the environment of an aetiological factor(s) for epilepsy which acts in the perinatal period disrupting the neurodevelopment.

Adolescent↗

PubMed1993

Does prenatal influenza divert susceptible females from later affective psychosis to schizophrenia?

We examined the relationship between influenza epidemics and the number of schizophrenic and affective psychotic individuals born each month between 1938 and 1965 in England and Wales. Increased death rates from influenza were followed 5 months later by a significant increase in schizophrenic births and a concurrent fall in the number of births of affective psychotic individuals. When the sexes were examined separately, both the positive effect of influenza on schizophrenic births and its negative effect on affective psychotic births were evident for females but not for males. Furthermore, during February to June in high influenza years, there was an inverse relationship between the number of female schizophrenic and affective psychotic births. The explanation for these surprising findings may be that prenatal exposure to influenza impairs the neurodevelopment of some females with a predisposition to affective psychosis, in such a way that their later illness shows schizophrenic rather than affective features.

Adult↗

PubMed1995

An association study of a neurotrophin-3 (NT-3) gene polymorphism with schizophrenia.

Since abnormalities of brain development play a role in the aetiology of schizophrenia, growth factors, known to play a role in neurodevelopment, such as neurotrophin-3 (NT-3), are therefore candidate genes for this disorder. The A3/147 bp allele of a dinucleotide repeat polymorphism in the promoter region of the NT-3 gene has been reported as occurring more frequently in a sample of Japanese schizophrenics compared to controls. We have determined the frequency of alleles of this polymorphism in 175 Caucasian schizophrenic patients and 147 control subjects. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and, in a test of allalleles, the patients and controls did not differ significantly in allele frequencies. However, the male schizophrenics were more likely than male controls to have the A3/147 bp allele (P = 0.029).

Alleles↗

PubMed1999

Cognition and neuropathology in schizophrenia.

Clinical, neuropsychological and neuropathological avenues of research have advanced in concert to increase our understanding of schizophrenia. Progress in four general areas of investigation will be reviewed: (i) fronto-temporal-limbic dysfunction; (ii) abnormal connectivity or 'miswiring'; (iii) aberrant neurodevelopment; and (iv) neurodegeneration and neural injury. The challenge for post-mortem research is to identify the molecular pathways in which abnormalities culminate in the highly diverse features of the disorder. Candidate pathways must be able to account for the developmental and deteriorative clinical profiles and the global and focal neuropsychological deficits, as well as the various patho-anatomical abnormalities that indicate aberrant cytoarchitecture and connectivity in the absence of neurodegeneration or other obvious evidence of postmaturational neural injury.

Brain↗

PubMed2006

Evidence for abnormal early development in a mouse model of Rett syndrome.

Rett syndrome (RTT) is a neurodevelopmental disorder that affects mainly females, associated in most cases to mutations in the MECP2 gene. After an apparently normal prenatal and perinatal period, patients display an arrest in growth and in psychomotor development, with autistic behaviour, hand stereotypies and mental retardation. Despite this classical description, researchers always questioned whether RTT patients did have subtle manifestations soon after birth. This issue was recently brought to light by several studies using different approaches that revealed abnormalities in the early development of RTT patients. Our hypothesis was that, in the mouse models of RTT as in patients, early neurodevelopment might be abnormal, but in a subtle manner, given the first descriptions of these models as initially normal. To address this issue, we performed a postnatal neurodevelopmental study in the Mecp2(tm1.1Bird) mouse. These animals are born healthy, and overt symptoms start to establish a few weeks later, including features of neurological disorder (tremors, hind limb clasping, weight loss). Different maturational parameters and neurological reflexes were analysed in the pre-weaning period in the Mecp2-mutant mice and compared to wild-type littermate controls. We found subtle but significant sex-dependent differences between mutant and wild-type animals, namely a delay in the acquisition of the surface and postural reflexes, and impaired growth maturation. The mutant animals also show altered negative geotaxis and wire suspension behaviours, which may be early manifestations of later neurological symptoms. In the post-weaning period the juvenile mice presented hypoactivity that was probably the result of motor impairments. The early anomalies identified in this model of RTT mimic the early motor abnormalities reported in the RTT patients, making this a good model for the study of the early disease process.

Animals↗

PubMed2006

Dopaminergic deficiency in mice with reduced levels of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A, Dyrk1A(+/-).

The dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) gene encodes a protein kinase known to play a critical role in neurodevelopment. Mice with one functional copy of Dyrk1A (Dyrk1A(+/-)) display a marked hypoactivity and altered gait dynamics in basal conditions and in novel environments. Dopamine (DA) is a key neurotransmitter in motor behavior and genetic deletion of certain genes directly related to the dopaminergic system has a strong impact on motor activity. We have studied the effects of reduced Dyrk1A expression on the function of the nigrostriatal dopaminergic system. To characterize the dopaminergic system in DYRK1A(+/-) mice, we have used behavioral, pharmacological, histological, neurochemical and neuroimaging (microPET) techniques in a multidisciplinary approach. Dyrk1A(+/-) mice exhibited decreased striatal DA levels, reduced number of DA neurons in the substantia nigra pars compacta, as well as altered behavioral responses to dopaminergic agents. Moreover, microdialysis experiments revealed attenuated striatal DA release and positron emission tomography scan display reduced forebrain activation when challenged with amphetamine, in Dyrk1A(+/-) compared with wild-type mice. These data indicate that Dyrk1A is essential for a proper function of nigrostriatal dopaminergic neurons and suggest that Dyrk1A(+/-) mice can be used to study the pathogenesis of motor disorders involving dopaminergic dysfunction.

Animals↗