Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice. (9/1034)

1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.  (+info)

Contact between people with learning disability and general practitioners: a cross-sectional case note survey. (10/1034)

BACKGROUND: This paper describes primary care consultation rates in a sample of people with learning disability. The study was carried out as part of a wider survey of primary care for this population group in response to concerns over quality of care and debate between general practitioners (GPs) and the local health authority over the need for additional remuneration for caring for people with learning disability. Estimates of consultation rates in the literature to date are conflicting and we sought to provide local data on the number and type of contacts with the primary care teams to inform this debate. METHOD: A primary care case note review was carried out of 112 people with learning disability aged over 18, identified from an administrative sample of 967 people known to health and social services. Contact rates (with practice nurses or GPs) were calculated and indirectly standardized for age using data from the fourth National Morbidity Survey in General Practice (MSGP4). RESULTS: Standardized consultation ratio in men was 156 (95 per cent confidence interval (CI) 142-172), in women was 111 (95 per cent CI 102-121) and for both sexes was 127 (95 per cent CI 120-135). Average contact rate was 4.6 per person per year. Eighty per cent of contacts were with GPs. Eighteen per cent (95 per cent CI 11-25 per cent) of subjects consulted, on average, more than once every two months. Limited information on underlying cause of learning disability and severity was available. Consultation rates were independent of age and sex, and were not increased in people with Down's syndrome or epilepsy compared with the rest of the sample population. Consultation rates were highest in people living in staffed group homes (p = 0.01). The presence of special arrangements between practices and residential facilities did not appear to increase service contact, but this finding is prone to measurement bias. CONCLUSIONS: Contrary to the findings of previous studies, people with learning disability consult primary care teams more frequently than the general population. However, this should not be taken as supporting calls for additional resources without addressing the effectiveness and appropriateness of health care offered.  (+info)

Cranial magnetic resonance imaging and school performance in very low birth weight infants in adolescence. (11/1034)

AIM: To determine whether neurological deficits are associated with structural anomalies of the brain in very low birthweight (VLBW) infants with subsequent learning disorders but without cerebral palsy, or whether other factors, such as poor early growth, are responsible. METHODS: Eighty seven VLBW infants and eight term controls who had been examined at school between the ages of 12 and 13 years, had cranial magnetic resonance imaging (MRI) scans at 15-17 years of age. RESULTS: Thirty seven (42.5%) of the VLBW children had abnormalities reported on their scans (two porencephaly, 28 periventricular leucomalacia, 24 ventricular dilatation, and 15 thinning of the corpus callosum). No significant differences in intelligence quotient, motor clumsiness, or frequency of attention deficit / hyperactivity disorder were observed between those children with MRI lesions and those with normal scans. Quantitative measurements showed the VLBW infants had smaller brains, and a relatively smaller corpus callosum compared with controls. No association between brain measurements and school performance was observed among the VLBW infants. CONCLUSIONS: The difficulties experienced by VLBW children at school are unlikely to be the result of perinatal brain injury, but they might to be attributable to the effects of poor postnatal growth.  (+info)

Reduced K+ channel inactivation, spike broadening, and after-hyperpolarization in Kvbeta1.1-deficient mice with impaired learning. (12/1034)

A-type K+ channels are known to regulate neuronal firing, but their role in repetitive firing and learning in mammals is not well characterized. To determine the contribution of the auxiliary K+ channel subunit Kvbeta1.1 to A-type K+ currents and to study the physiological role of A-type K+ channels in repetitive firing and learning, we deleted the Kvbeta1.1 gene in mice. The loss of Kvbeta1.1 resulted in a reduced K+ current inactivation in hippocampal CA1 pyramidal neurons. Furthermore, in the mutant neurons, frequency-dependent spike broadening and the slow afterhyperpolarization (sAHP) were reduced. This suggests that Kvbeta1.1-dependent A-type K+ channels contribute to frequency-dependent spike broadening and may regulate the sAHP by controlling Ca2+ influx during action potentials. The Kvbeta1.1-deficient mice showed normal synaptic plasticity but were impaired in the learning of a water maze test and in the social transmission of food preference task, indicating that the Kvbeta1.1 subunit contributes to certain types of learning and memory.  (+info)

Deficits in memory tasks of mice with CREB mutations depend on gene dosage. (13/1034)

Studies in Aplysia, Drosophila, and mice have shown that the transcription factor CREB is involved in formation and retention of long-term memory. To analyze the impact of differential CREB levels on learning and memory, we varied the gene dosage of CREB in two strains of mutant mice: (1) CREBalphadelta mice, in which the alpha and delta isoforms are disrupted, but a third isoform beta is strongly up-regulated; (2) CREBcomp, a compound strain with one alphadelta allele and one CREBnull allele in which all CREB isoforms are disrupted. To minimize genetic background effects, CREB mutations were backcrossed into a C57BL/6 and a FVB/N strain, respectively, and studies were performed in F1 hybrids from these lines. CREBcomp but not CREBalphadelta F1 hybrids were impaired in water maze learning and fear conditioning, demonstrating a CREB gene dosage effect. However, analysis of the platform searching strategies in the water maze task suggested that CREBcomp mutants are impaired in behavioral flexibility rather than in spatial memory. In contrast to previous experiments using CREBalphadelta mice with different genetic background, the F1 hybrid CREBalphadelta and CREBcomp mice did not show deficits in a social transmission of food preference task nor in dentate gyrus and CA1 LTP as recorded from slice preparations. These data indicate that the hybrid vigor typical for F1 hybrids may compensate for a reduction in CREB levels in some tests. On the other hand, the persistence of clear behavioral deficits as shown by the F1 hybrid CREBcomp mice in water maze and fear conditioning indicates a robust and repeatable phenomenon that will permit further functional analysis of CREB.  (+info)

Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta1 receptor gene. (14/1034)

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor beta (TRbeta) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRbeta gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRbeta gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRbeta gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.  (+info)

Impaired capacity of cerebellar patients to perceive and learn two-dimensional shapes based on kinesthetic cues. (15/1034)

This study addresses the issue of the role of the cerebellum in the processing of sensory information by determining the capability of cerebellar patients to acquire and use kinesthetic cues received via the active or passive tracing of an irregular shape while blindfolded. Patients with cerebellar lesions and age-matched healthy controls were tested on four tasks: (1) learning to discriminate a reference shape from three others through the repeated tracing of the reference template; (2) reproducing the reference shape from memory by drawing blindfolded; (3) performing the same task with vision; and (4) visually recognizing the reference shape. The cues used to acquire and then to recognize the reference shape were generated under four conditions: (1) "active kinesthesia," in which cues were acquired by the blindfolded subject while actively tracing a reference template; (2) "passive kinesthesia," in which the tracing was performed while the hand was guided passively through the template; (3) "sequential vision," in which the shape was visualized by the serial exposure of small segments of its outline; and (4) "full vision," in which the entire shape was visualized. The sequential vision condition was employed to emulate the sequential way in which kinesthetic information is acquired while tracing the reference shape. The results demonstrate a substantial impairment of cerebellar patients in their capability to perceive two-dimensional irregular shapes based only on kinesthetic cues. There also is evidence that this deficit in part relates to a reduced capacity to integrate temporal sequences of sensory cues into a complete image useful for shape discrimination tasks or for reproducing the shape through drawing. Consequently, the cerebellum has an important role in this type of sensory information processing even when it is not directly associated with the execution of movements.  (+info)

Phenotype of adults with the 22q11 deletion syndrome: A review. (16/1034)

22q11 deletion syndrome (22qDS) is due to microdeletions of chromosome region 22q11.2. Little is known about the phenotype of adults. We reviewed available case reports of adults (age >/=18 years) with 22qDS and compared the prevalence of key findings to those reported in a large European survey of 22qDS (497 children and 61 adults) [Ryan et al., 1997: J. Med. Genet. 34:798-804]. Fifty-five studies reported on 126 adults (83 women, 40 men, 3 unknown sex), mean age 29.6 years (SD = 8.7 years). Compared with the European survey, adults with 22qDS reviewed had a lower rate of CHD, 30% versus 75%; chi(2) = 88.65, df = 1, P < 0.0001, but higher rates of identified palate anomalies, 88% versus 15%; chi(2) = 37.45, df = 1, P < 0.0001, and learning difficulties, 94% versus 79%; chi(2) = 12.13, df = 1, P = < 0.0008. The most common finding reported was minor facial anomalies. Few reports provided details of minor physical anomalies. Psychiatric conditions were more prevalent, 36% versus 18%; chi(2)= 5.71, df = 1, P < 0.02, than in the survey: 60% of reviewed adults were transmitting parents (72% mothers) ascertained following diagnosis of affected offspring. They had lower rates of CHD, cleft palate, and psychiatric disorders but similar rates of learning disabilities, and other palate and facial anomalies compared with adults ascertained by other methods. The results suggest that learning disabilities and facial and palate anomalies may be key findings in 22qDS adults, but that ascertainment is a key factor in the observed phenotype. Comprehensive studies of adults with 22qDS identified independently of familial transmission are necessary to further delineate the phenotype of adults and to determine the natural history of the syndrome.  (+info)