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PubMed2006

Aspirin is a substrate for paraoxonase-like activity: implications in atherosclerosis.

Paraoxonase 1 (PON 1) is an enzyme that is promiscuous in its ability to hydrolyze various types of substrates. It hydrolyzes aryl esters, phosphate esters, lactones, and reduces lipid peroxides to hydroxides. Aspirin is an aryl ester with a short plasma half life. We hypothesized that aspirin would be effectively hydrolyzed by PON 1 and many of its anti-atherogenic effects, at least in part, could be accounted for by its antioxidant product, salicylic acid. In this study, we determined the ability of human plasma and PON 1-rich HDL to hydrolyze acetyl ester of salicylic acid (aspirin). The ability of aspirin to compete for the hydrolysis of paraoxon and p-nitrophenylacetate was determined. In addition, nitrated aspirin was synthesized and tested directly for hydrolysis. Aspirin competed for the hydrolysis of paraoxon and p-nitrophenylacetate by HDL in a dose-dependent manner. Human plasma and HDL were also able to hydrolyze nitroaspirin and aspirin and release nitrosalicylic acid and salicylic acid, respectively. These findings suggest that salicylic acid might be generated in the plasma from aspirin. The ability of long-term treatment with aspirin to retard atherosclerosis might be dependent on the generation of free salicylic acid, a scavenger of free radicals.

Adult↗
PubMed2004

Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate in the liver.

Senescence marker protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases androgen-independently with aging. We have now characterized a unique property of SMP30, the hydrolysis of diisopropyl phosphorofluoridate (DFP), which is similar to the chemical warfare nerve agents sarine, soman and tabun. Hydrolysis of DFP was stimulated equally well by 1 mM MgCl2, MnCl2 or CoCl2, to a lesser extent by 1 mM CdCl2 but not at all by 1 mM CaCl2. No 45Ca2+-binding activity was detected for purified SMP30, suggesting that SMP30 is not a calcium-binding protein, as others previously stated. Despite the sequence similarity between SMP30 and a serum paraoxonase (PON), the inability of SMP30 to hydrolyze PON-specific substrates such as paraoxon, dihydrocoumarin, gamma-nonalactone, and delta-dodecanolactone indicate that SMP30 is distinct from the PON family. We previously established SMP30 knockout mice and have now tested DFPase activity in their livers. The livers from wild-type mice contained readily detectable DFPase activity, whereas no such enzyme activity was found in livers from SMP30 knockout mice. Moreover, the hepatocytes of SMP30 knockout mice were far more susceptible to DFP-induced cytotoxicity than those from the wild-type. These results indicate that SMP30 is a unique DFP hydrolyzing enzyme in the liver and has an important detoxification effect on DFP. Consequently, a reduction of SMP30 expression might account for the age-associated deterioration of cellular functions and enhanced susceptibility to harmful stimuli in aged tissue.

Aging↗
PubMed2004

First principles of the MameLuke multi-actor modelling framework for land use change, illustrated with a Philippine case study.

This paper presents the first principles of the MameLuke framework, an agent-based modelling framework for studying environmental issues and land use and cover change (LUCC). The MameLuke framework enhances the understanding of the relationship between societal processes and LUCC by modelling individual and group decisions and human-environment interactions. The framework allows for the transformation of real-life stories into computerised models following a predetermined sequence. By doing so, the framework allows for a truly integrative approach, because it is not bound to any particular scientific discourse. Even better, the framework enables its users to combine scientific discourses regarding human decisions and behaviour on multiple scales and levels. The agents (actors and locations) in the framework are heterogeneous. This heterogeneity of agent behaviour is established by dividing the agents into categories. If an agent is a member of an agent category or combination of categories, it has access to a defined set of implementable actions. The actions are constructed out of potential option paths (POPs) and potential option nodes (PONs). The whole of POPs represent a theoretical construct of agent behaviour and decisions that the framework user wishes to explore. The POP defines a sequence of PONs. The PON is a transaction interface between an initialising agent and a recipient agent where they exchange material and immaterial capital. This paper explains the basic architecture of the MameLuke framework and shows its applicability with a model of a Philippine case study. This case study concerns the dynamics of migration and deforestation. It is part of a larger study on land use change in the San Mariano watershed area at the forest fringe of the Sierra Madre mountains in the Philippines.

Conservation of Natural Resources↗
PubMed2004

Vestibulo-reticular projections in adult lamprey: their role in locomotion.

This study describes the anatomical projections from vestibular secondary neurons to reticulospinal neurons in the adult lamprey and the modulation of vestibular inputs during fictive locomotion. Anatomical tracers were applied in the posterior (PRRN) and middle rhombencephalic reticular nuclei as well as to the proximal stumps of cut vestibular nerve branches to identify the neurons projecting to the reticular nuclei that were in close proximity with vestibular primary afferents. Labeled neurons were found in the intermediate (ION) and posterior (PON) octavomotor nuclei, and were more numerous on the side of the injection (around 56-87 and 101-107 for the ION and the PON, respectively). Morphologies varied but cells were mostly round or oval. Axonal projections from the PON formed a dense bundle, whereas those from the ION were less densely packed. Based on their morphology and the distribution of their projections, most vestibulo-reticular neurons were presumed to be vestibulospinal cells. Reticulospinal cells from the PRRN were recorded intracellularly in the in vitro brainstem-spinal cord preparation and large excitatory post-synaptic potentials (EPSPs) were evoked following stimulation of the ipsilateral anterior and the contralateral posterior branches of the vestibular nerves, whereas inhibitory post-synaptic potentials (IPSPs) or smaller EPSPs were elicited by stimulation of the ipsilateral posterior or of the contralateral anterior branches. During fictive locomotion, both the excitatory and the inhibitory responses displayed phasic changes in amplitude such that the amplitude of the EPSPs was minimal when the spinal cord activity switched from the ipsilateral to the contralateral side of the recorded reticulospinal cell. The IPSPs were then of maximal amplitude. We propose that this modulation could serve to reduce the influence of vestibular inputs in response to head movements during locomotion.

Animals↗
PubMed2005

Nitric oxide from the laterodorsal tegmental neurons: its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons.

Nitric oxide released from the cholinergic neurons in the pons may play important roles in sleep-wake regulation. However, there are few reports demonstrating the mechanisms of nitric oxide release in the cholinergic neurons in the pons. The present study investigated the effects of drug delivery of N-methyl-D-aspartic acid on nitric oxide and the neurotransmitters released in the laterodorsal tegmental nucleus (LDT), one of the major cholinergic cell groups in the pons, in rats by in vivo microdialysis with a view to clarifying nitric oxide functions in the cholinergic system. The application of N-methyl-D-aspartic acid (1 mM) into the LDT induced a significant increase in NO(2)and NO(3) for 40 min (P<0.001). Furthermore the same dose of N-methyl-D-aspartic acid induced a significant increase in cyclic GMP for 30 min (P<0.05), as well as in acetylcholine (P<0.001) and norepinephrine for 15 min (P<0.001). 3-(4-Morpholinyl)-sydonone imine hydrochloride (a nitric oxide donor, 5 mM) also induced significant increase in norepinephrine (P<0.05). Pretreatment with 1 mM 2-amino-5-phosphonopentanoic acid (an antagonist of N-methyl-D-aspartic acid receptor) prevented the N-methyl-D-aspartic acid-induced increase in cyclic GMP (P<0.01), acetylcholine and norepinephrine (P<0.01), while that with 1 mM N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) prevented the increase in cyclic GMP (P<0.01) and norepinephrine (P<0.01) but not in acetylcholine. These results suggested that nitric oxide release in the LDT induced by activation of the N-methyl-D-aspartic acid receptor on the cholinergic neurons of the LDT, then through the cyclic GMP system, facilitates norepinephrine release from the terminals of noradrenergic neurons in the locus coeruleus. Based on these findings, we propose a possible role of nitric oxide in the LDT is as a retrograde regulator of norepinephrine release from the locus coeruleus.

Acetylcholine↗
PubMed2005

Sensorimotor gating, orienting and social perception in schizophrenia.

Basic neurocognition and social cognition appear to influence the social impairments of persons with schizophrenia. This study examined relationships between two very basic automatic processes (i.e., sensorimotor gating and orienting) and social perception in schizophrenic patients. Thirty outpatients with schizophrenia completed psychophysiological measures of sensorimotor gating (prepulse inhibition, PPI), orienting (prepulse facilitation, PPF), and social perception (the Half Profile of Nonverbal Sensitivity, Half PONS). A median split was used to divide patients into poor and good gaters and poor and good orienters. Analyses revealed that patients with good PPI scored significantly higher on the Half PONS than patients with poor PPI. PPI showed a significant correlation (r=-0.54) with Half PONS performance, indicating that schizophrenia patients who were better able to gate out competing stimuli (i.e., less startle) were also better at detecting relevant social cues. Orienting (PPF) and social perception were not related. This study is the first to our knowledge to demonstrate an association between sensorimotor gating and social perception. The findings are consistent with other studies that have demonstrated relationships between basic neurocognition and social cognition. By showing a link between sensorimotor gating and social perception, this study supports social cognition's potential role as a mediator of the relationship between neurocognition and social functioning in schizophrenia.

Adult↗
PubMed2004

[Cavernous haemangiomas: hearing and vestibular inaugural symptoms].

INTRODUCTION: Cavernous haemangiomas (cavernomas)(CH) are relatively rare (2% of cranial tumoral pathology) vascular malformations mostly observed in the central nervous system. Their most common topographical site in brain stem is midline in the pons, for which clinical course may mimic symptoms of peripheral origin (sudden deafness, fluctuating hearing loss, Meniere-like vertigo). AIM: To establish the correlation between the clinical manifestations of hearing and balance disturbance and the anatomical site within the pons of cavernous haemangiomas, and to describe their clinical features, and the findings on auditory brainstem response (ABR) and magnetic resonance imaging (MRI). To propose a literature review about CH and its implications. MATERIAL AND METHOD: We made a retrospective review of the histories of three patients aged 24, 44 and 45 years, diagnosed as having cavernomas of the brainstem in which audiometric evaluation, videonystagmography (VNG), ABR and imaging techniques lead to the diagnosis of intracranial cavernoma. RESULTS: The clinical and radiological files were reviewed and a direct relationship between symptoms and localization was found in all 3 patients, especially in relation to our understanding of the auditory and vestibular pathways within the brainstem. CONCLUSION: The literature regarding cavernomas of the pons is reviewed and the clinical, neuroimage, pathological, natural course and management aspects of the disease are discussed. We recommend the use of cerebral MRI for initial diagnosis which shows a typical rosette-like appearance with a heterogeneous signal on T2-weighted images, along with follow-up and investigation into similar profiles among family members. At present there is no consensus about the treatment to follow when cavernomas are located in the brain stem. There is no specific medical treatment for this condition, and surgery is indicated only exceptionally. Anticoagulant therapy, platelet-dispersing medication and violent sports activities are contraindicated.

Adult↗
PubMed2001

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.

Adult↗
PubMed2000

[123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder.

BACKGROUND: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([(123)I]-beta-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [(123)I]-beta-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [(123)I]-beta-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients. METHODS: Depressed SAD patients and healthy control subjects were investigated using [(123)I]-beta-CIT SPECT 4 hours and again 24 hours after tracer injection. Subjects had either never used psychotropic medication or had been drug-free for at least 6 months prior to the investigation. Specific-to-nondisplaceable partition coefficient (V(3)") was calculated for the thalamus-hypothalamus and the midbrain-pons; the cerebellum served as a reference region. RESULTS: Patients showed a reduction in V(3)" in thalamus-hypothalamus (2.41+/-0.3 vs. 2.84+/-0.4; p = .026) 24 hours post tracer injection (p.i.). No difference between patients and control subjects was found in midbrain-pons (1.31+/-0.2 vs. 1.42+/-0.2; p = .39). No differences were detected in the SPECT acquisitions 4 hours p.i. CONCLUSIONS: Depressed SAD patients showed lower specific-to-nondisplaceable [(123)I]-beta-CIT binding in the region of interest (ROI) thalamus-hypothalamus. The small size of the midbrain-pons ROI may have contributed to the failure to show a difference in this ROI as well. Similar to reduced midbrain 5-HTT availability in nonseasonal depression, depression in SAD seems to be associated with reduced 5-HTT availability to the thalamus-hypothalamus.

Adult↗
PubMed1999

Tryptophan residue(s) as major components of the human serum paraoxonase active site.

Serum paraoxonase (PON1, EC 3.1.8.1.) is a high density lipid- (HDL)-associated, calcium-dependent enzyme whose 3D structure, active site residues and physiological substrates are not known. The kinetic parameters k(cat) and Km (relative to k(cat) and Km of the wild-type), determined with four substrates (phenylacetate, paraoxon, diazoxon and chlorpyrifosoxon) were less than 1, and more than 100% for the W280A and W280F mutant enzymes, respectively. These results indicated that the aromatic/hydrophobic character of the amino acid in position 280 is essential for PON1 activity. In this study, we investigated whether this aromatic residue is in the PON1 active site. Group-specific labelling studies with N-bromosuccinimide, an oxidative agent of tryptophan, strongly suggested that one or several Trp could be in the active site of PON1 but we could not conclude either on the specificity of the labelling reaction or on the number of oxidized Trp. However, although PON activity was not altered by the hydrophilic tryptophan-modifying reagent 2-hydroxy-5-nitrobenzyl chloride (NBC), it was significantly reduced by the p-nitrophenylacetate analog 2-acetoxy-5-nitrobenzyl chloride (ANBC), whose hydrolysis by PON1 generated NBC in the active site. Moreover, since at least one calcium ion is present in the PON catalytic site, we attempted to probe the metal local environment using the calcium analog terbium. The luminescence spectrum of the PON terbium complex exhibited an emission peak at 545 nm characteristic of an aromatic residue (Trp and/or Tyr)-terbium interaction. In conclusion, both the results obtained with the mechanism-based inhibitor of PON1 (ANBC) and the calcium-binding site luminescent probe terbium support the hypothesis of the presence of at least one Trp residue in the PON1 active site. Trp residue(s) may be involved in the binding of aromatic substrates.

Acetates↗
PubMed1999

Regional differences in genetic subgroup frequency in hereditary cerebellar ataxia, and a morphometrical study of brain MR images in SCA1, MJD and SCA6.

Molecular genetic assessments of 69 individuals in 44 families with hereditary cerebellar ataxia (HCA) were made to determine the relative frequencies of subtypes of HCA in Yamagata, Japan. Fifteen families (34%) had SCA1, none had SCA2, nine (20%) had MJD, five (11%) had SCA6 and nine (20%) had DRPLA. These findings differ markedly from those in other regions of Japan and the rest of the world. A morphometrical study of the brain MR images also was made on 38 individuals with SCA1 (n = 14), MJD (n = 8) or SCA6 (n = 16). In SCA1, the ventral pons was atrophic in proportion to the amount of cerebellar atrophy. In MJD, both the pons and the cerebellum were atrophic, cerebellar atrophy being less pronounced than that in SCA1 and SCA6. While both the major and minor axes of the ventral pons were proportionally decreased in SCA1, the minor axis was more decreased than the major axis in MJD. In SCA6, a mild reduction in the ratio of the ventral pontine area to the posterior fossa area (Pv/PF) was observed as well as obvious cerebellar atrophy. These findings indicate that in MR images SCA1, MJD and SCA6 show different atrophic features of the cerebellum and brainstem.

Adult↗
PubMed1998

Evidence for involvement of the subcoeruleus nucleus and nucleus raphe magnus in urine storage and penile erection in decerebrate rats.

PURPOSE: Micturition and male sexual activity require the lower urinary tract to function. During the sexual act, micturition must be inhibited and urine stored in the bladder. We studied the role of the brainstem in relation to both micturition/urine storage and penile erection in rats. MATERIALS AND METHODS: Wire electrodes were placed on the dorsal nerve of the penis and microelectrodes for stimulation were introduced into the brainstem in decerebrate male rats. Electrical stimulation was used to locate optimally responding sites by monitoring the isovolumetric intravesical pressure and intracavernous pressure. RESULTS: Electrical stimulation of the dorsal nerve of the penis, the subcoeruleus nucleus in the rostral pons, and the nucleus raphe magnus in the caudal pons increased intracavernous pressure, but inhibited rhythmic bladder contractions. Electrical stimulation of Barrington's nucleus (the pontine micturition center in the rat) in the rostral pons induced bladder contraction. Stimulation of the pontine reticular formation did not increase intracavernous pressure. Acute transection of the thoracic spinal cord eliminated rhythmic bladder contractions, but gave rise to sporadic increments of intracavernous pressure. CONCLUSIONS: This electrophysiological study demonstrated that the subcoeruleus nucleus and nucleus raphe magnus are involved in both urine storage and penile erection, and that their physiological functions are reciprocally controlled; so that erection leads to inhibition of micturition.

Animals↗
PubMed2003

Serum paraoxonase activity decreases in rheumatoid arthritis.

OBJECTIVE: To estimate the alterations of paraoxonase 1 (PON1) and high-density lipoprotein (HDL) in rheumatoid arthritis (RA). DESIGN AND METHODS: We investigated the serum enzyme activity and concentration of PON1 and their relationship with serum lipids, high-density lipoprotein (HDL) parameters, and acute phase reactants of serum amyloid A (SAA) and C-reactive protein (CRP) in patients with RA. RESULTS: Serum paraoxonase (PON) activity was significantly decreased in RA patients (n = 64, 131 +/- 53 micro mol/min/L) compared with healthy subjects (n = 155, 164 +/- 59) despite the absence of any difference in serum lipid levels between the two groups. This decrease of serum PON activity in RA patients was found in every genotype (Q/Q, Q/R, R/R) of PON1 at 192 Q/R. There was a different distribution in PON1 Q/R genotypes between RA patients and healthy subjects, and RA patients exhibited less (44%) positive PON1-Q than did the healthy subjects (66%). In a further investigation of age- and gender-matched subgroups of RA (n = 25) and healthy subjects (n = 25), not only serum PON activity, but also lecithin-cholesterol acyltransferase (LCAT) was found to be significantly decreased in RA patients (125 +/- 61 micro mol/min/L, 63.2 +/- 17.2 nmol/ml/hr/37 degrees C) than in healthy subjects (169 +/- 67, 74.7 +/- 19.5), respectively. PON1 and LCAT as well as HDL constituent apolipoprotein (apo) AI and apo AII, were altered significantly in RA patients. CONCLUSIONS: Acute-phase HDL, which is remodeled structurally and functionally in RA, might be less anti-atherogenic due to the impairment of original HDL function. These alterations of HDL in RA patients may explain in part the reported increase in cardiovascular mortality in patients with RA.

Aged↗
PubMed2006

The pretectum: connections and oculomotor-related roles.

Research over the past two decades in mammals, especially primates, has greatly improved our understanding of the afferent and efferent connections of two retinorecipient pretectal nuclei, the nucleus of the optic tract (NOT) and the pretectal olivary nucleus (PON). Functional studies of these two nuclei have further elucidated some of the roles that they play both in oculomotor control and in relaying oculomotor-related signals to visual relay nuclei. Therefore, following a brief overview of the anatomy and retinal projections to the entire mammalian pretectum, the connections and potential roles of the NOT and the PON are considered in detail. Data on the specific connections of the NOT are combined with data from single-unit recording, microstimulation, and lesion studies to show that this nucleus plays critical roles in optokinetic nystagmus, short-latency ocular following, smooth pursuit eye movements, and adaptation of the gain of the horizontal vestibulo-ocular reflex. Comparable data for the PON show that this nucleus plays critical roles in the pupillary light reflex, light-evoked blinks, rapid eye movement sleep triggering, and modulating subcortical nuclei involved in circadian rhythms.

Animals↗
PubMed1997

Activities of monoamine oxidase (MAO) A and B in discrete regions of rat brain after rapid eye movement (REM) sleep deprivation.

Rapid eye movement (REM) sleep deprivation increases monoaminergic (noradrenergic and serotonergic) turnover and their metabolites in whole brain of rats. This increase in metabolites may indicate increased activity of the enzymes responsible for the inactivation of monoamines. To test this hypothesis, we assayed the activity of monoamineoxidases (MAOs) A and B in hippocampus, hypothalamus, brainstem and its divisions pons and medulla oblongata in rats deprived of REM sleep for 96 h. REM sleep deprivation was carried out by the flower-pot technique. A control group remained in their home cages. MAO A was assayed by using [14C]-5-hydroxytryptamine as the substrate (50 microM final concentration) and MAO B by using [14C]-beta-phenylethylamine (2 microM final concentration). The enzymes were assayed in the mitochondrial fraction.The results obtained showed that a significant decrease in the activity of MAO A was obtained in the brainstem and an increase in medulla oblongata and no statistical differences in the activity of MAO B in brainstem, pons and medulla oblongata and MAO A in pons; there were also no differences in the activities of both MAO A and B in hippocampus and hypothalamus. Although our results confirmed previous data regarding changes in MAO A activity in brainstem and medulla oblongata, they did not confirm our hypothesis that the increase in monamine turnover and metabolites in the brain would be the result of increased MAO activity.

Animals↗
PubMed2003

Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity.

The whole brain free fatty acid (FFA) level, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were determined in the frontal cortex, cerebellum, hippocampus, and pons-medulla region of the single pentylenetetrazol (PZT)-treated and PZT-kindled Hannover-Wistar rats. PZT administration in the convulsive dose caused significant increase of the brain FFA content. Decreased SOD activity was detected in the frontal cortex of PZT-kindled rats, whereas decreased GPX activity was found in the frontal cortex and cerebellum of all treated rats, as well as in the hippocampus and pons-medulla of PZT-kindled rats. Kindling caused distinctive change of antioxidative defense in the frontal cortex, hippocampus, and pons-medulla region.

Animals↗
PubMed2002

Aluminium-induced changes in the rat brain serotonin system.

Aluminium exposure, apart from producing cholinotoxicity, can include changes in other neurotransmitter levels since neurotransmitter levels are closely interrelated. Reports of aluminium (Al) effects on brain neurotransmitters are limited. To investigate the effect of Al on the rat brain serotonergic system, the present study was conducted to explore brain region-specific changes and duration-specific changes. Male Wistar albino rats were exposed orally to Al chloride (AlCl(3).6H(2)O; 320 mg/kg body weight) daily for up to 60 days and changes in the 5-hydroxytrytamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) levels were observed after 4, 14 and 60 days of exposure in olfactory lobe (OLB), cerebellum (CBL), pons (PON), medulla oblongata (MOB), spinal cord (SPI), hypothalamus (HYP), hippocampus (HIP), striatum (STR), midbrain (MBR) and cortex (COR) brain regions. Significantly increased 5-HT levels observed in brain regions OLB (60 days), HIP (4,14 days), STR (14 days), HYP (14, 60 days), MBR (4 and 14 days), PON (4 days), MOB (4 days) and SPI (4, 14 and 60 days) following Al exposure may be due to Al deactivating 5-HT system by decreased release and subsequent breakdown of 5-HT. Decreased 5-HT levels observed in cerebral COR, HIP (60 days) and in CBL after 4 and 60 days of exposure suggest an inhibitory effect of Al on the 5-HT system due to withdrawal of cholinergic input in these brain regions. 5-HIAA level changes correlate with 5-HT level changes in many brain regions studied. The results reveal that the neurochemical changes due to Al were dependent on the duration of exposure and are brain-region-specific. The observed changes may be related to the cholinergic toxicity of Al.

Aluminum↗
PubMed1998

Neurogenesis of patterns of automatic ventilatory activity.

Normal respiration, termed eupnea, is characterized by periodic filling and emptying of the lungs. Eupnea can occur 'automatically' without conscious effort. Such automatic ventilation is controlled by the brainstem respiratory centers of pons and medulla. Following removal of the pons, eupnea is replaced by gasping, marked by brief but maximal inspiratory efforts. The mechanisms by which the respiratory rhythms are generated have been examined intensively. Evidence is discussed that ventilatory activity can be generated in multiple regions of pons and medulla. Eupnea and gasping represent fundamentally different ventilatory patterns. Only for gasping has a critical region for neurogenesis been identified, in the rostral medulla. Gasping may be generated by the discharge of 'pacemaker' neurons. In eupnea, this pacemaker activity is suppressed and incorporated into the pontile and medullary neuronal circuit responsible for the neurogenesis of eupnea. Evidence for ventilatory neurogenesis which has been obtained from a number of in vitro preparations is discussed. A much-used preparation is that of a 'superfused' brainstem of the neonatal rat. However, activities of this preparation differ greatly from those of eupnea, as recorded in vitro or in arterially perfused in vitro preparations. Activities of this 'superfused' preparation are identical with gasping and, hence, results must be reinterpreted accordingly. The possibility is present that mechanisms responsible for generating respiratory rhythms may differ from those responsible for shaping respiratory-modulated discharge patterns of cranial and spinal nerves. The importance of pontile mechanisms in the neurogenesis and control of eupnea is reemphasized.

Animals↗