Biomedical subjects

Lauri Alanko

Publications and source records attributed to Lauri Alanko.

9 recordsLinked to original sources

PubMed2006

Localization of equilibrative nucleoside transporters in the rat brain.

Adenosine is a recognized inhibitory neuromodulator and neuroprotective agent in the central nervous system. It is produced both intra- and extracellularly and transported across the cell membrane. Nucleoside transporters thus have a major impact on the extracellular adenosine levels, and consequently adenosine signalling. We have raised and characterized polyclonal antibodies against both the equilibrative nucleoside transporters 1 and 2, and report for the first time their distribution in rat brain at the cellular level. Double staining studies were performed to assess the localization of the transporters in neural and glial cells. Both transporters were present in practically all neurons. Some astrocytes showed equilibrative nucleoside transporter 1 staining, while equilibrative nucleoside transporter 2 staining on astrocytes was observed only sporadically.

Animals↗

PubMed2005

Actigraphic assessment of sleep in young adults with Asperger syndrome.

A high prevalence of subjective insomnia in adults with Asperger syndrome has been reported. In the present study the sleep quality of these patients was studied using wrist actigraphy. Nineteen adults with Asperger syndrome and frequent feelings of insomnia were compared with 10 controls devoid of neuropsychiatric disorders and subjective sleep problems during six consecutive nights. The patients had similar actigraphic sleep profile to the controls. The subjective low sleep quality in patients was not reflected in actigraphic assessment of sleep. This finding suggests that pervasive anxiety inherent in persons with Asperger syndrome predisposes them to insomnia complaints.

Adult↗

PubMed2004

The effect of age on prepro-orexin gene expression and contents of orexin A and B in the rat brain.

Orexin A and B (hypocretin 1 and 2) are hypothalamic peptides, which are synthesized in the lateral hypothalamus. Orexins participate in the regulation energy balance, food intake, vigilance and several endocrine and autonomic functions. The widespread projections of the orexin neurons suggest that they may have a role in coordination of different brain activities. The effects of ageing on the orexin system have not been studied previously. Prepro-orexin gene expression in the lateral hypothalamus, and the contents of orexin A and B peptides in the lateral hypothalamus and hypothalamus were measured in young, middle-aged and old (3, 12 and 24 months) rats. In the course of ageing, the expression of the prepro-orexin gene and the levels of orexin A and B decreased; the main decrease occurred by 12 months. Sleep deprivation for 6h increased slightly the expression of prepro-orexin gene in young rats. Deterioration of the orexin system may play a role in the phenomenon associated with aging, e.g. decreased consolidation of vigilance states, endocrine changes and dysfunctions of autonomic nervous system.

Aging↗

PubMed2003

Insomnia is a frequent finding in adults with Asperger syndrome.

BACKGROUND: Asperger syndrome (AS) is a neurodevelopmental disorder belonging to autism spectrum disorders with prevalence rate of 0,35% in school-age children. It has been most extensively studied in childhood while there is scarcity of reports concerning adulthood of AS subjects despite the lifelong nature of this syndrome. In children with Asperger syndrome the initiation and continuity of sleep is disturbed because of the neuropsychiatric deficits inherent of AS. It is probable that sleep difficulties are present in adulthood as well. Our hypothesis was that adults with AS suffer from difficulty in initiating and maintaining sleep and nonrestorative sleep (insomnia). METHODS: 20 AS without medication were compared with 10 healthy controls devoid of neuropsychiatric anamnesis. Clinical examination, blood test battery and head MRI excluded confounding somatic illnesses. Structured psychiatric interview for axis-I and axis-II disorders were given to both groups as well as Beck Depression Inventory and Wechsler adult intelligence scale, revised version.Sleep quality was assessed with sleep questionnaire, sleep diary during 6 consecutive days and description of possible sleep problems by the participants own words was requested. RESULTS: compared with controls and with normative values of good sleep, AS adults had frequent insomnia. In sleep questionnaire 90% (18/20), in sleep diary 75% (15/20) and in free description 85% (17/20) displayed insomnia. There was a substantial psychiatric comorbidity with only 4 AS subject devoid of other axis-I or axis-II disorders besides AS. Also these persons displayed insomnia. It can be noted that the distribution of psychiatric diagnoses in AS subjects was virtually similar to that found among patient with chronic insomnia. CONCLUSIONS: the neuropsychiatric deficits inherent of AS predispose both to insomnia and to anxiety and mood disorders. Therefore a careful assessment of sleep quality should be an integral part of the treatment plan in these individuals. Conversely, when assessing adults with chronic insomnia the possibility of autism spectrum disorders as one of the potential causes of this condition should be kept in mind.

Adult↗

PubMed2003

Adenosine, energy metabolism, and sleep.

While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness. The key molecule in the induction of sleep appears to be adenosine, which induces sleep locally in the basal forebrain.

Adenosine↗

PubMed2003

Adenosine kinase and 5'-nucleotidase activity after prolonged wakefulness in the cortex and the basal forebrain of rat.

The effect of prolonged wakefulness on adenosine kinase (AK), ecto-5'-nucleotidase and endo-5'-nucleotidase activity was assessed in the present study. Rats were sleep deprived for 3 or 6h, and one group was allowed to sleep 2h of recovery sleep after the 6h deprivation. The cortex and the basal forebrain were dissected, and frozen rapidly on dry ice. The enzyme activity of adenosine kinase was measured by monitoring the conversion of [2-3H]-adenosine into [3H]-adenosine monophosphate (AMP) and the ecto-5'-nucleotidase and endo-5'-nucleotidase activities by monitoring the conversion of [2-3H]-AMP into [3H]-adenosine. The enzyme activities did not change during deprivation or recovery sleep in either cortex or basal forebrain when compared to unhandled controls. Significant diurnal variation in enzyme activities was noted in both brain areas. In the basal forebrain adenosine kinase and both nucleotidases showed their lowest activity in the middle of the rest phase, 6h after lights on, suggesting a low level of adenosine metabolism, both production and degradation at this time point. In the cortex adenosine kinase had a diurnal activity pattern similar to the basal forebrain and the ecto-5'-nucleotidase activity was low already early in the rest phase, 3h after lights on, and remained low until the end part of the rest phase, 8h after lights on. Endo-5'-nucleotidase lacked diurnal variation. These activity patterns may be associated with the lower level of energy metabolism during sleep compared to wakefulness.

5'-Nucleotidase↗

PubMed2003

Nitrobenzylthioinosine (NBMPR) binding and nucleoside transporter ENT1 mRNA expression after prolonged wakefulness and recovery sleep in the cortex and basal forebrain of rat.

We have previously shown that extracellular adenosine levels increase locally in the basal forebrain (BF) during prolonged wakefulness, yet the cellular mechanisms of this local accumulation have remained unknown. The extracellular adenosine levels are strictly regulated by adenosine metabolism and its transport through cell membrane by the nucleoside transporters. As we previously showed that the key adenosine metabolizing enzymes were not affected by prolonged wakefulness, we now focussed on potential changes in the nucleoside transporters. In the present study, we measured the binding of nitrobenzylthioinosine (NBMPR), an ENT1 transporter inhibitor, and the ENT1 transporter mRNA after prolonged wakefulness and recovery sleep. Rats were sleep-deprived for 3 or 6 h using gentle handling. After 6 h one group was allowed to sleep for 2 h. NBMPR binding was determined from BF and cortex by incubating tissue extracts with [3H] NBMPR. The in situ hybridization was carried out on 20 microm cryosections using [35S]dATP-labelled oligonucleotide probe for ENT1 mRNA. The NBMPR binding was significantly decreased in the BF, but not in the cortex, after 6 h sleep deprivation when compared with the time-matched controls, suggesting a decline in adenosine transport. The expression of ENT1 mRNA did not change during prolonged wakefulness or recovery sleep in either cortex or the BF, although circadian variations were measured in both areas. We conclude that the regional decrease in adenosine transport could contribute to the gradual accumulation of extracellular adenosine in the basal forebrain during prolonged wakefulness.

Adenosine↗

PubMed2003

Local energy depletion in the basal forebrain increases sleep.

Sleep saves energy, but can brain energy depletion induce sleep? We used 2,4-dinitrophenol (DNP), a molecule which prevents the synthesis of ATP, to induce local energy depletion in the basal forebrain of rats. Three-hour DNP infusions induced elevations in extracellular concentrations of lactate, pyruvate and adenosine, as well as increases in non-REM sleep during the following night. Sleep was not affected when DNP was administered to adjacent brain areas, although the metabolic changes were similar. The amount and the timing of the increase in non-REM sleep, as well as in the concentrations of lactate, pyruvate and adenosine with 0.5-1.0 mM DNP infusion, were comparable to those induced by 3 h of sleep deprivation. Here we show that energy depletion in localized brain areas can generate sleep. The energy depletion model of sleep induction could be applied to in vitro research into the cellular mechanisms of prolonged wakefulness.

2,4-Dinitrophenol↗

PubMed2002

Adenosine and sleep.

Adenosine is directly linked to the energy metabolism of cells. In the central nervous system an increase in neuronal activity enhances energy consumption as well as extracellular adenosine concentrations. In most brain areas high extracellular adenosine concentrations, through A(1) adenosine receptors, decrease neuronal activity and thus the need for energy. Adenosine seems to act as a direct negative feed-back inhibitor of neuronal activity. Hypoxia and ischemia induce very high extracellular adenosine levels, which may limit further brain damage. In brain areas that regulate cortical vigilance, particularly in the basal forebrain, high extracellular adenosine concentrations, induced by prolonged wakefulness, decrease the activity of presumably cholinergic cells and via this mechanism promote sleep. Our hypothesis is that in the cholinergic basal forebrain prolonged wakefulness induces local energy depletion that generates increases in extracellular adenosine concentrations in this area. In addition to the immediate effects, high extracellular adenosine concentrations also induce intracellular changes in signal transduction and transcription, e.g. increase in A(1) receptor expression and NF-kappaB binding activity. These changes may at least partially mediate the long term effects of prolonged wakefulness. Adenosine may also be a common mediator of the effects of several other sleep-inducing factors.

Adenosine↗