Deficits In Adulthood Research Articles

Exposure to salient, dynamic sensory stimuli during development increases distractibility in adulthood.

It has been suggested that excessive exposure of children to the dynamic and highly salient audio-visual stimuli conveyed by electronic media may induce attention-related deficits in adulthood. This study was designed to evaluate this hypothesis in a controlled animal model setup. Building on their natural responsiveness to odors, we exposed juvenile rats for 1 h daily to a dynamic series of interchanging, highly salient odors, while controls were exposed to a non-changing mixture of these odors. Upon reaching adulthood, we tested the attentional capacity of the rats and measured their brain-derived neurotrophic factor (BDNF) levels as a proxy of neuronal plasticity. As compared with controls, rats exposed to the dynamic stimulation showed no attentional deficits under baseline task conditions, but their performance was dramatically impaired when an auditory distractor was introduced in the task. In addition, BDNF levels in the dorsal striatum of these rats were significantly increased relative to controls. These findings provide first empirical evidence that a continuous exposure to dynamic, highly salient stimuli has long-term effects on attentional functions later in life, and that these effects may have neural correlates in the dorsal striatum.

Female children with incarcerated adult family members at risk for lifelong neurological decline

abstractA secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99 (60%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their life-span.

Chronic NMDA receptor blockade in early postnatal period, but not in adulthood, impairs methamphetamine-induced conditioned place preference in rats

Early postnatal glutamatergic N-methyl-d-aspartate (NMDA) receptor blockade in animals is known to produce various behavioral deficits in adulthood. In the present study rats postnatally (day 7–20) treated chronically with MK-801, an NMDA receptor antagonist, were tested later in adulthood in methamphetamine (MAP)-induced conditioned place preference (CPP) using a unbiased procedure in a three-compartment apparatus. Rats with the same chronic treatment in adulthood were also tested. CPP test consisted of a baseline test before conditioning, place conditioning, and a preference test after conditioning. Rats postnatally treated with MK-801 did not show any evidence of preference for MAP-paired compartment compared with that for unpaired one in the preference test that was shown in rats postnatally treated with saline. On the other hand, rats treated with MK-801 in adulthood were not affected by the treatment and showed significant CPP as was shown in saline-treated control animals. Results suggest the possibility that chronic early postnatal, but not adulthood, NMDA receptor blockade induces persistent deficit of subsequent appetitive classical conditioning.

Multiple Anesthetic Exposure in Infant Monkeys Alters Emotional Reactivity to an Acute Stressor

Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive deficits in adulthood. The authors addressed the question of whether repeated postnatal anesthetic exposure was sufficient to cause long-term behavioral changes in a highly translationally relevant rhesus monkey model, allowing study of these variables against a background of protracted nervous system and behavioral development. Rhesus monkeys of both sexes underwent either three 4-h exposures to sevoflurane anesthesia (anesthesia group n = 10) or brief maternal separations (control group n = 10) on postnatal day 6 to 10 that were repeated 14 and 28 days later. Monkeys remained with their mothers in large social groups at all times except for overnight observation after each anesthetic/control procedure. At 6 months of age, each monkey was tested on the human intruder paradigm, a common test for emotional reactivity in nonhuman primates. The frequency of anxiety-related behaviors was significantly higher in monkeys that were exposed to anesthesia as neonates as compared with controls: anesthesia 11.04 ± 1.68, controls 4.79 ± 0.77, mean ± SEM across all stimulus conditions. Increased emotional behavior in monkeys after anesthesia exposure in infancy may reflect long-term adverse effects of anesthesia.

Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

Neonatal white matter injury (nWMI) is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P) 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2–3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life, followed by dysmyelination, abnormal spinal neuron composition, and neuro-motor deficits in adulthood.

Npas4 deficiency increases vulnerability to juvenile stress in mice

During specific windows of postnatal brain development, individuals are particularly susceptible to developing mental illnesses in adulthood. Adolescence is such a window during which environmental stress can have long-lasting consequences on social and cognitive functions. In individuals, highly vulnerable to stress, a relatively mild stressful situation can trigger the onset of psychiatric conditions. The genetic factors and mechanisms underlying vulnerability to stress are not well understood. Here, we show that variations in expression of the brain-specific transcription factor Npas4 contributes to the long-term consequences of juvenile stress on cognitive abilities. We observed that transgenic Npas4-deficient mice exposed to chronic mild stress during adolescence (but not during adulthood) develop prefrontal cortex-dependent cognitive deficits in adulthood, while the same stress did not affect Npas4 wild-type mice. These cognitive deficits were accompanied by fewer neuroblasts in the subventricular zone, and reduced ability of these immature neuronal cells to migrate away from this neurogenic zone toward cortical regions. These findings suggest for the first time that the transcription factor Npas4 could play a significant role in coping with juvenile stress. They also suggest that Npas4 could modulate resilience or vulnerability to stress by mediating the effects of stress on neurogenesis.

Spelling impairments in Spanish dyslexic adults.

Spelling deficits have repeatedly been observed in children with dyslexia. However, the few studies addressing this issue in dyslexic adults have reported contradictory results. We investigated whether Spanish dyslexics show spelling deficits in adulthood and which components of the writing production process might be impaired in developmental dyslexia. In order to evaluate the involvement of the lexical and the sublexical routes of spelling as well as the graphemic buffer, lexical frequency, phonology-to-orthography consistency and word length were manipulated in two writing tasks: a direct copy transcoding task and a spelling-to-dictation task. Results revealed that adults with dyslexia produced longer written latencies, inter-letter intervals, writing durations and more errors than their peers without dyslexia. Moreover, the dyslexics were more affected by lexical frequency and word length than the controls, but both groups showed a similar effect of P-O consistency. Written latencies also revealed that while the dyslexics initiated the response later in the direct copy transcoding task than in the spelling-to-dictation task, the controls showed the opposite pattern. However, the dyslexics were slower than the controls in both tasks. Results were consistent with the hypothesis that spelling difficulties are present in adults with dyslexia, at least in a language with a transparent orthography such as Spanish. These difficulties seem to be associated with a deficit affecting both lexical processing and the ability to maintain information about the serial order of the letters in a word. However, the dyslexic group did not differ from the control group in the application of the P-O conversion procedures. The spelling impairment would be in addition to the reading deficit, leading to poorer performance in direct copy transcoding compared to spelling-to-dictation.

Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults.

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about thepersistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

Dissociation in the Effects of Induced Neonatal Hypoxia-Ischemia on Rapid Auditory Processing and Spatial Working Memory in Male Rats

Infants born prematurely are at risk for cardiovascular events causing hypoxia-ischemia (HI; reduced blood and oxygen to the brain). HI in turn can cause neuropathology, though patterns of damage are sometimes diffuse and often highly variable (with clinical heterogeneity further magnified by rapid development). As a result, though HI injury is associated with long-term behavioral and cognitive impairments in general, pathology indices for specific infants can provide only limited insight into individual prognosis. The current paper addresses this important clinical issue using a rat model that simulates unilateral HI in a late preterm infant coupled with long-term behavioral evaluation in two processing domains - auditory discrimination and spatial learning/memory. We examined the following: (1) whether deficits on one task would predict deficits on the other (suggesting that subjects with more severe injury perform worse across all cognitive domains) or (2) whether domain-specific outcomes among HI-injured subjects would be uncorrelated (suggesting differential damage to orthogonal neural systems). All animals (sham and HI) received initial auditory testing and were assigned to additional auditory testing (group A) or spatial maze testing (group B). This allowed within-task (group A) and between-task (group B) correlation. Anatomic measures of cortical, hippocampal and ventricular volume (indexing HI damage) were also obtained and correlated against behavioral measures. Results showed that auditory discrimination in the juvenile period was not correlated with spatial working memory in adulthood (group B) in either sham or HI rats. Conversely, early auditory processing performance for group A HI animals significantly predicted auditory deficits in adulthood (p = 0.05; no correlation in shams). Anatomic data also revealed significant relationships between the volumes of different brain areas within both HI and shams, but anatomic measures did not correlate with any behavioral measure in the HI group (though we saw a hippocampal/spatial correlation in shams, in the expected direction). Overall, current data provide an impetus to enhance tools for characterizing individual HI-related pathology in neonates, which could provide more accurate individual prognoses within specific cognitive/behavioral domains and thus improved patient-specific early interventions.

Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea.

Children and adults with obstructive sleep apnea syndrome (OSAS) exhibit neurobehavioral abnormalities, but few studies have evaluated the transitional stage of adolescence. Obesity is also associated with neurobehavioral abnormalities, and many patients with OSAS are obese. However, the confounding effect of obesity on neurobehavioral abnormalities in adolescents with OSAS has not been evaluated. We hypothesized that obese adolescents with OSAS would exhibit more neurobehavioral abnormalities than obese and lean adolescents without OSAS. Cross-sectional, case control. Sleep Center and community. Obese adolescents with OSAS compared to (1) nonsnoring, obese controls without OSAS, and (2) nonobese, nonsnoring controls. Neurobehavioral evaluation. Obese adolescents with OSAS had significantly worse executive function and attention compared to both obese (P < 0.001) and lean (P < 0.001) controls, and more depression (P = 0.004) and externalizing symptoms than lean controls (P = 0.008). A higher percentage of participants in the OSAS group scored in the clinically abnormal range on executive functioning, attention, sleepiness, and behavioral functioning than lean controls. Mediation analyses indicated that level of sleep apnea significantly mediated the effect of body mass on executive functioning, attention, and behavior. Obese adolescents with OSAS show impaired executive and behavioral function compared to obese and lean controls, and are more likely to score in the clinically abnormal range on measures of neurobehavioral functioning. These results are especially concerning given that the frontal lobe is still developing during this critical age period. We speculate that untreated OSAS during adolescence may lead to significant neurobehavioral deficits in adulthood.

Early life stress and hippocampal neurogenesis in the neonate: sexual dimorphism, long term consequences and possible mediators.

Adverse early life experience decreases adult hippocampal neurogenesis and results in increased vulnerability to neuropsychiatric disorders. Despite that the effects of postnatal stress on neurogenesis have been widely studied in adult individuals, few efforts have been done to evaluate its immediate effects on the developing hippocampus. Moreover, it is not clear whether postnatal stress causes a differential impact in hippocampus development in male and female neonates that could be related to emotional deficits in adulthood. It has been proposed that the long term effects of early stress exposure rise from a persistent HPA axis activation during sensitive time windows; nevertheless the exact mechanisms and mediators remain unknown. Here, we summarize the immediate and late effects of early life stress on hippocampal neurogenesis in male and female rat pups, compare its later consequences in emotionality, and highlight some relevant mediator peptides that could be potentially involved in programming.

Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: Implications for schizophrenia

The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing kynurenine (100 mg/day; progeny = EKYNs) from ED15 until ED22. Controls were fed an unadulterated mash (progeny = ECONs). The dietary loading procedure elevated maternal and fetal plasma kynurenine (2223% and 693% above controls, respectively) and increased fetal KYNA (forebrain; 500% above controls) on ED21. Elevations in forebrain KYNA disappeared after termination of the loading (PD2), but KYNA levels in the prefrontal cortex (PFC) were unexpectedly increased again when measured in adults (PD56–80; 75% above controls). We also observed changes in several markers of prefrontal excitability, including expression of the α7nAChR (22% and 17% reductions at PD2 and PD56–80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56–80), dendritic spine density (11–14% decrease at PD56–80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ.

Neonatal anoxia in rats: Hippocampal cellular and subcellular changes related to cell death and spatial memory

Neonatal anoxia in rodents has been used to understand brain changes and cognitive dysfunction following asphyxia. This study investigated the time-course of cellular and subcellular changes and hippocampal cell death in a non-invasive model of anoxia in neonatal rats, using Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL) to reveal DNA fragmentation, Fluoro-Jade® B (FJB) to show degenerating neurons, cleaved caspase-3 immunohistochemistry (IHC) to detect cells undergoing apoptosis, and transmission electron microscopy (TEM) to reveal fine ultrastructural changes related to cell death. Anoxia was induced by exposing postnatal day 1 (P1) pups to a flow of 100% gaseous nitrogen for 25min in a chamber maintained at 37°C. Control rats were similarly exposed to this chamber but with air flow instead of nitrogen. Brain changes following anoxia were evaluated at postnatal days 2, 14, 21 and 60 (P2, P14, P21 and P60). In addition, spatial reference memory following anoxia and control treatments was evaluated in the Morris water maze, starting at P60. Compared to their respective controls, P2 anoxic rats exhibited (1) higher TUNEL labeling in cornus ammonis (CA) 1 and the dentate gyrus (DG), (2) higher FJB-positive cells in the CA2–3, and (3) somato-dendritic swelling, mitochondrial injury and chromatin condensation in irregular bodies, as well as other subcellular features indicating apoptosis, necrosis, autophagy and excitotoxicity in the CA1, CA2–3 and DG, as revealed by TEM. At P14, P21 and P60, both groups showed small numbers of TUNEL-positive and FJB-positive cells. Stereological analysis at P2, P14, P21 and P60 revealed a lack of significant differences in cleaved caspase-3 IHC between anoxic and control subjects. These results suggest that the type of hippocampal cell death following neonatal anoxia is likely independent of caspase-3 activation. Neonatal anoxia induced deficits in acquisition and performance of spatial reference memory in the Morris water maze task. Compared to control subjects, anoxic animals exhibited increased latencies and path lengths to reach the platform, as well as decreased searching specifically for the platform location. In contrast, no significant differences were observed for swimming speeds and frequency within the target quadrant. Together, these behavioral results indicate that the poorer performance by anoxic subjects is related to spatial memory deficits and not to sensory or motor deficits. Therefore, this model of neonatal anoxia in rats induces hippocampal changes that result in cell losses and impaired hippocampal function, and these changes are likely related to spatial memory deficits in adulthood.

116. Sex differences in microglial morphology and number: Implications for function and behavior

Males and females exhibit marked differences in prevalence and age of onset of neuropsychiatric disorders. Males are more likely to have disorders that arise early in life (e.g. autism), whereas females exhibit disorders arising around puberty (e.g. depression). No sex-based neurobiological differences have been described that can explain this sexual dimorphism. We show that male rats and mice have increased numbers of microglia in the hippocampus (HP) at postnatal day 4 (P4) than females. Neonatally-infected male rats also display cognitive deficits in adulthood when subjected to a systemic lipopolysaccharide (LPS) injection that induces an exaggerated IL-1β response within the HP of these rats. On the contrary, females are protected from this inflammatory response and cognitive deficit. Microglia play a critical role in synaptic pruning during neurodevelopment. Thus, increased numbers of microglia in neonatal male compared to female mice during critical stages of early synapse formation and maturation may adversely subject males to early-life infection by affecting synaptic pruning function of microglia. Insufficient or excess synaptic pruning due to inflammatory microglia may have enduring consequences on behavior and cognition in adulthood. Ongoing studies are aimed at determining the underlying mechanism behind heightened susceptibility of males by using Cx3cr1 -cre x MyD88 -flox mice, as well as investigating differences in synaptic pruning abilities of male vs. female microglia either in the presence or absence of immune challenge.

Interaction of Early Life Stress and Corticotropin-Releasing Hormone Receptor Gene: Effects on Working Memory

Early life stress (ELS) experience is associated with persisting working memory (WM) deficits; changes to the corticotropin-releasing hormone (CRH) system; and structural, functional, and epigenetic changes in the hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS experience to predict depression as well as neuroendocrine and neuronal reactivity. Although these findings indicate that vulnerable genotypes might also show impaired WM performance after ELS experience, no previous study investigated whether there is an interaction effect of CRHR1 polymorphisms and ELS experience on WM performance. Subjects (N = 451) were genotyped for rs110402 and rs242924 within the CRHR1 gene. We used an n-back task to investigate the hypothesis that WM performance in healthy subjects may be subtly influenced by functional differences in CRHR1 and represents an early marker of increased vulnerability after exposure to ELS. Exposure to ELS had a particularly strong impact on WM performance in subjects with the common homozygous GG GG genotype, whereas only severe exposure to ELS interfered with WM accuracy in AT carriers. Our data indicate that specific CRHR1 polymorphisms moderate the effect of ELS experience on WM performance. Exposure to ELS in combination with a vulnerable genotype results in subtle memory deficits in adulthood, which might develop before psychopathological symptoms.

Effects of moderate prenatal ethanol exposure and age on social behavior, spatial response perseveration errors and motor behavior

Persistent deficits in social behavior are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked deficits in social behavior following moderate prenatal alcohol exposure (PAE) in the rat to functional alterations in the ventrolateral frontal cortex [21]. In addition to social behaviors, the regions comprising the ventrolateral frontal cortex are critical for diverse processes ranging from orofacial motor movements to flexible alteration of behavior in the face of changing consequences. The broader behavioral implications of altered ventrolateral frontal cortex function following moderate PAE have, however, not been examined. In the present study we evaluated the consequences of moderate PAE on social behavior, tongue protrusion, and flexibility in a variant of the Morris water task that required modification of a well-established spatial response. PAE rats displayed deficits in tongue protrusion, reduced flexibility in the spatial domain, increased wrestling, and decreased investigation, indicating that several behaviors associated with ventrolateral frontal cortex function are impaired following moderate PAE. A linear discriminant analysis revealed that measures of wrestling and tongue protrusion provided the best discrimination of PAE rats from saccharin-exposed control rats. We also evaluated all behaviors in young adult (4–5 months) or older (10–11 months) rats to address the persistence of behavioral deficits in adulthood and possible interactions between early ethanol exposure and advancing age. Behavioral deficits in each domain persisted well into adulthood (10–11 months), however, there was no evidence that aging enhances the effects of moderate PAE within the age ranges that were studied.

Peer pressures: Social instability stress in adolescence and social deficits in adulthood in a rodent model

Studies in animal models generate and test hypotheses regarding developmental stage-specific vulnerability that might inform research questions about human development. In both rats and humans, peer relationships are qualitatively different in adolescence than at other stages of development, and social experiences in adolescence are considered important determinants of adult social function. This review describes our adolescent rat social instability stress model and the long-lasting effects social instability has on social behaviour in adulthood as well as the possible neural underpinnings. Effects of other adolescent social stress experiences in rats on social behaviours in adulthood also are reviewed. We discuss the role of hypothalamic–pituitary–adrenal (HPA) function and glucocorticoid release in conferring differential susceptibility to social experiences in adolescents compared to adults. We propose that although differential perception of social experiences rather than immature HPA function may underlie the heightened vulnerability of adolescents to social instability, the changes in the trajectory of brain development and resultant social deficits likely are mediated by the heightened glucocorticoid release in response to repeated social stressors in adolescence compared to in adulthood.

A Pilot Examination of Self-Esteem, Depression, and Sleep in College Women

While sleep deficits in adulthood are common and worsening, college women experience significantly more sleep problems and depression than their male counterparts. In recent years, sleep has been investigated as one of the primary contributors to college functioning and GPA. No known study, however, has investigated the connection between self-esteem, depression and sleep. Questionnaire assessments were given to 43 female college juniors and seniors, including: demographic information, Rosenberg Self-esteem Scale, Beck Depression Inventory, and Pittsburg Quality Sleep Index. This pilot study investigates the relationship between college self-esteem and sleep quality, as mediated by depression. The results of the study indicate that self-esteem predicts both depression and sleep quality, such that decreased levels of self-esteem are associated with higher levels of depression and decreased sleep quality. Moreover, depression also predicts sleep quality and serves to mediate the relation between self-esteem and sleep quality. The results suggest that students’ self-esteem plays a significant role in the experience of depression, and that depression is the primary mechanism through which self-esteem influences sleep.

Impaired working memory by repeated neonatal MK-801 treatment is ameliorated by galantamine in adult rats

Early life blockade of the NMDA receptor by using MK-801, a non-competitive NMDA receptor antagonist, induces behavioral changes that mimic several features of schizophrenia. In the current study, we first examined the effects of neonatal MK-801 treatment in male Sprague-Dawley rats on locomotor activity, prepulse inhibition and spatial working memory in adolescence (postnatal day 35, PND35) and adulthood (PND63). Next, we investigated the effects of an acetylcholinesterase inhibitor, galantamine, on working memory deficits induced by MK-801 treatment. Rats were treated with either saline or MK-801 (0.25mg/kg twice daily) at PND 5–14, and the long-term behavioral effects were investigated. MK-801 treated rats showed moderate working memory impairments in adolescence but a pronounced deficit in adulthood. However, locomotion and prepulse inhibition at two life stages were not affected by this treatment. Systemic administration of galantamine (1mg/kg) 30min before each training session significantly improved neonatal MK-801-induced working memory deficits in adulthood. In conclusion, these results suggest that the neonatal MK-801 treatment-induced selective working memory deficit is related to a change in brain cholinergic systems.

Irreversible airway obstruction in adulthood after bronchiolitis in infancy: Evidence from a 30-year follow-up study

Lower respiratory infections in infancy may be associated with lung function deficits in adulthood. Our aim was to evaluate lung function, with a special focus on irreversible airway obstruction, thirty years after bronchiolitis or pneumonia in infancy. In 1981-1982, 83 children under two years of age were hospitalized for bronchiolitis and 44 for pneumonia at Kuopio University Hospital, Finland. In 2010, 47 bronchiolitis patients, 22 pneumonia patients and 138 controls attended the study, including spirometry before (pre-BD) and after bronchodilatation (post-BD). The measured indices were forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), that were presented as % of predicted value (FVC% and FEV1%). FEV1/FVC was presented as both absolute FVC/FEV1-ratio and % of predicted (FEV1/FVC%). Irreversible airway obstruction was defined as post-BD FEV1/FVC% below 88% of predicted (FEV1/FVC% <88%) according to Finnish reference values or FEV1/FVC-ratio below fifth percentile (FEV1/FVC <5th percentile), according to Global Lung Function Initiative reference values. All lung function indices were lower in former bronchiolitis patients and pre- and post-BD FEV1% in pneumonia patients, compared to controls. 21% of bronchiolitis (OR, 95%CI; 5.59, 1.72-18.21) and 9% of pneumonia patients (2.24, 0.34-13.56) had FEV1/FVC% <88% compared to controls (4%). Likewise 7 (15%) of bronchiolitis (7.07, 1.33-37.22) and 1 (5%) of pneumonia patients (1.73, 0.12-24.77) had FEV1/FVC <5th percentile compared to controls 2 (1%). Evidence of reduced lung function was present 30 years after hospitalization for bronchiolitis or pneumonia in infancy. Irreversible airway obstruction after severe bronchiolitis in infancy suggests permanent, structural alterations in airways.