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Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio.

We have examined the effects of mildly oxidized LDL and atherosclerosis on the levels of two proteins associated with HDL; apolipoprotein J (apoJ), and paraoxonase (PON). On an atherogenic diet, PON activity decreased by 52%, and apoJ levels increased 2.8-fold in fatty streak susceptible mice, C57BL/6J (BL/6), but not in fatty streak resistant mice, C3H/HeJ (C3H). Plasma PON activity was also significantly decreased, and apoJ levels were markedly increased in apolipoprotein E knockout mice on the chow diet, resulting in a 9.2-fold increase in the apoJ/PON ratio as compared to controls. Furthermore, a dramatic increase in the apoJ/PON ratio (over 100-fold) was observed in LDL receptor knockout mice when they were fed a 0.15%-cholesterol-enriched diet. Injection of mildly oxidized LDL (but not native LDL) into BL/6 mice (but not in C3H mice) on a chow diet resulted in a 59% decrease in PON activity (P < 0.01) and a 3.6-fold increase in apoJ levels (P < 0.01). When an acute phase reaction was induced in rabbits, or the rabbits were placed on an atherogenic diet, hepatic mRNA for apoJ was increased by 2.7-fold and 2.8-fold, respectively. Treatment of HepG2 cells in culture with mildly oxidized LDL (but not native LDL) resulted in reduced mRNA levels for PON (3.0-fold decrease) and increased mRNA levels for apoJ (2.0-fold increase). In normolipidemic patients with angiographically documented coronary artery disease who did not have diabetes and were not on lipid-lowering medication (n = 14), the total cholesterol/HDL cholesterol ratio was 3.1+/-0.9 as compared to 2.9+/-0.4 in the controls (n = 19). This difference was not statistically significant. In contrast, the apoJ/PON ratio was 3.0+/-0.4 in the patients compared to 0.72+/-0.2 in the controls (P < 0.009). In a subset of these normolipidemic patients (n = 5), the PON activity was low (48+/-6.6 versus 98+/-17 U/ml for controls; P < 0.009), despite similar normal HDL levels, and the HDL from these patients failed to protect against LDL oxidation in co-cultures of human artery wall cells. We conclude that: (a) mildly oxidized LDL can induce an increased apoJ/PON ratio, and (b) the apoJ/PON ratio may prove to be a better predictor of atherosclerosis than the total cholesterol/HDL cholesterol ratio.

Animals↗

Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions.

Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei) are involved in the generation of rapid eye movement (REM) sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase), the enzyme which inactivates acetylcholine (Ach) in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase) are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex) after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min(-1) mg protein(-1)) were assayed photometrically. The results (mean +/- SD) obtained showed a statistically significant (Student t-test) increase in total Achase activity in the pons (control: 147.8 +/- 12.8, REM sleep-deprived: 169.3 +/- 17.4, N = 6 for both groups, P<0.025) and thalamus (control: 167.4 +/- 29.0, REM sleep-deprived: 191.9 +/- 15.4, N = 6 for both groups, P<0.05). Increases in membrane-bound Achase activity in the pons (control: 171.0 +/- 14.7, REM sleep-deprived: 189.5 +/- 19.5, N = 6 for both groups, P<0.05) and soluble enzyme activity in the medulla oblongata (control: 147.6 +/- 16.3, REM sleep-deprived: 163.8 +/- 8.3, N = 6 for both groups, P<0.05) were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity induced by REM sleep deprivation was specific to the pons, a brain region where cholinergic neurons involved in REM generation are located, and also to brain regions which receive cholinergic input from the pons (the thalamus and medulla oblongata). During REM sleep extracellular levels of Ach are higher in the pons, medulla oblongata and thalamus. The increase in Achase activity in these brain areas after REM sleep deprivation suggests a higher rate of Ach turnover.

Acetylcholinesterase↗

MR imaging of the normal and abnormal clivus.

We retrospectively reviewed 330 T1-weighted sagittal images, 80 T2-weighted sagittal images, and 83 gadopentetate-dimeglumine-enhanced scans of normal adults to determine the MR appearance of the normal adult clivus. MR images of 21 patients with an abnormal clivus (19 with tumor invasion and two with marrow reconversion) were also evaluated retrospectively and compared with those of the control group to assess MR features distinguishing the two groups. Our study revealed that a normal adult clivus consisted of low- and high-intensity portions mixed in various proportions on T1-weighted images. The low-intensity portion was isointense or hyperintense relative to the pons and always contained foci of bright signal intensity. The low-intensity tumor of a pathologic clivus tended to be hypointense relative to the pons (17/19), and was completely devoid of foci of bright signal intensity. The normal adult clivus was approximately isointense relative to the pons on T2-weighted images. Clival tumors were grossly hyperintense relative to the pons on T2-weighted images in 11 of 17 patients. In the remaining six patients, either a portion of or the entire lesion was isointense relative to the pons and, therefore, was not detectable on T2-weighted images. A normal adult clivus can enhance to some degree (19/83). Clival tumors were found to enhance intensely. A clivus of very low signal intensity (signal void) on T1- or T2-weighted images was always abnormal. The clivus with marrow reconversion was uniformly hypointense relative to the pons on T1-weighted images and isointense relative to normal marrow on T2-weighted images. The intensity patterns of the normal clivus on T1- and T2-weighted MR images change predictably with advancing age. Intensity patterns of abnormal clivi differ from those of normal clivi. When contrast material is used, normal and abnormal clivi generally show different patterns of enhancement.

Adult↗

[Effect of isoflurane anesthesia on norepinephrine metabolism in rat brain].

The author studied the effect of isoflurane anesthesia on norepinephrine (NE) metabolism in rat brain to elucidate a mechanism of anesthesia by measuring NE and its metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). Male Wistar rats weighing 230-270 g were anesthetized in a cage (42 x 27 x 19 cm3) with 2% isoflurane in air for 20 minutes. Rats were allocated to one of three groups randomly: unanesthetized control group (8 rats), anesthesia group (8 rats) and recovery group (8 rats). The rats were decapitated after only staying in the cage for 20 minutes in the control group, immediately after isoflurane anesthesia for 20 minutes in the anesthesia group and 20 minutes after recovery from anesthesia in the recovery group. Immediately after decapitation, their brains were rapidly dissected on the ice into the locus coeruleus, pons plus medulla oblongata, hypothalamus, thalamus, corpus striatum, midbrain, hippocampus, amygdala and cerebral cortex. NE and MHPG contents were determined by high pressure liquid chromatography. The NE contents of the pons plus medulla oblongata, hippocampus, and cerebral cortex increased significantly in the anesthesia group as compared with those of the control group. A significantly lower NE content was observed in the amygdala, and cerebral cortex of the recovery group as compared with that of the anesthesia group. The MHPG contents of the locus coeruleus, pons plus medulla oblongata, hypothalamus, and thalamus increased significantly in the recovery group as compared with those of the anesthesia group. The MHPG/NE ratio was calculated to determine NE turnover. The ratios of the locus coeruleus, pons plus medulla oblongata, thalamus, corpus striatum, and cerebral cortex decreased significantly in the anesthesia group as compared with the control group, while those of the locus coeruleus, pons plus medulla oblongata, hypothalamus, thalamus, and amygdala increased significantly in the recovery group as compared with the anesthesia group. The results obtained in the study suggest that a possible mechanism of isoflurane anesthesia in rat might be associated with decreased NE release in the locus coeruleus, pons, medulla oblongata and thalamus.

Anesthesia, Inhalation↗

[Relationship between the polymorphism of carboxylic esterases and genetic susceptibility to organophosphates pesticides exposure].

OBJECTIVE: To study the relationship between the polymorphism of butyrylcholinesterase (BChE, EC 3.1.1.8) and paraoxonase (PonE, EC 3.1.8.1), and the individuals' genetic susceptibility to organophosphates pesticides (OPs) exposure. METHODS: 75 OPs exposure workers were selected to determine their BChE-K, PON-192 and PON-55 genotypes using PCR-RFLP. The accumulative symptom scores and the whole blood acetylcholinesterase activity (mmol x h(-1) x ml(-1)) were used as health index. Firstly, the health condition related to single gene site of the three gene loci was analyzed to determine which kinds of genotype were susceptible. Then, used the multiple variance analysis was to see if there existed interactions among these three gene loci. Finally, established the multi-factor linear regression equation, in which considered some other factors that might influence the health situation such as age, gender and the exposure time. According to the equation, could get the accumulative symptom scores of each kind of subpopulation of different genotypes. RESULTS: The mean AChE activities of the exposed workers with BChE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) were 105.0 +/- 23.0, 84.4 +/- 16.4, 79.0 +/- 9.9, respectively; The accumulative symptom scores were 3.7 +/- 3.8, 9.2 +/- 3.0, 12.5 +/- 0.7, respectively. The AChE activities of the exposed workers with PON-192 genotype BB (37 cases), genotype AB (27 cases) and genotype AA (11 cases) were 116.8 +/- 15.1, 91.2 +/- 15.6, 72.3 +/- 21.4, respectively; The accumulative symptom scores were 2.0 +/- 3.2, 6.7 +/- 3.3, 9.7 +/- 1.8, respectively. Similarly, the AChE activities of the exposed workers with PON-55 genotype LL (70 cases) and genotype LM (5 cases) were 102.4 +/- 23.0, 82.8 +/- 22.0; The accumulative symptom scores were 4.5 +/- 4.2, 9.2 +/- 3.6, respectively. Single variance analysis showed that the accumulative symptom scores of the individuals with abnormal homozygote of these three gene loci were the highest, which indicated that they were most susceptible to OPs. Multiple variance analysis showed there were no interactions among the three gene loci. Age, gender and exposure time had no statistical significance, while genotypes of the three gene loci had statistical significance to health situation. CONCLUSION: Genotypes of BChE-K, PON-192 and PON-55 are related to susceptibility to OPs exposure.

Adult↗

Perioperative optic neuropathy following off-pump coronary artery bypass grafting.

Visual loss from ischemic perioperative optic neuropathy (PON) rarely occurs during the postoperative period of patients undergoing cardiac surgery. Since the first description, PON has been associated with cardiopulmonary bypass (CPB), being some CPB-related complications and epiphenomena considered the causes of such terrible complication. In particular, the risk for micro-embolization during aortic cannulation and clamping, the CPB-related inflammatory response, the hemodilution and the hypothermia during CPB could be responsible of PON. However, some cases of PON still remain idiopathic. We report here a very rare case of PON following off-pump surgery in a patient with severe coronary disease and multiorgan comorbidities. The case reported opens the debate on the potential mechanisms underlying PON, other than cardiopulmonary bypass.

Aged↗

MR imaging of the normal and abnormal clivus.

We retrospectively reviewed 330 T1-weighted sagittal images, 80 T2-weighted sagittal images, and 83 gadopentetate-dimeglumine-enhanced scans of normal adults to determine the MR appearance of the normal adult clivus. MR images of 21 patients with an abnormal clivus (19 with tumor invasion and two with marrow reconversion) were also evaluated restrospectively and compared with those of the control group to assess MR features distinguishing the two groups. Our study revealed that a normal adult clivus consisted of low- and high-intensity portions mixed in various proportions on T1-weighted images. The low-intensity portion was isointense or hyperintense relative to the pons and always contained foci of bright signal intensity. The low-intensity tumor of a pathologic clivus tended to be hypointense relative to the pons (17/19), and was completely devoid of foci of bright signal intensity. The normal adult clivus was approximately isointense relative to the pons on T2-weighted images. Clival tumors were grossly hyperintense relative to the pons on T2-weighted images in 11 of 17 patients. In the remaining six patients, either a portion of or the entire lesion was isointense relative to the pons and, therefore, was not detectable on T2-weighted images. A normal adult clivus can enhance to some degree (19/83). Clival tumors were found to enhance intensely. A clivus of very low signal intensity (signal void) on T1- or T2-weighted images was always abnormal. The clivus with marrow reconversion was uniformly hypointense relative to the pons on T1-weighted images and isointense relative to normal marrow on T2-weighted images.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Functional difference between the magnocellular neurosecretory nuclei of the rat hypothalamus].

The supraoptic, paraventricular, and postoptic nuclei (SON, PVN, and PON, respectively) of the hypothalamus were studied under conditions of 3 months training of rats to hypoxia (exposure for 6 h daily in a low pressure chamber under 7600m of simulated altitude). All the three nuclei were activated during the first 5 days, and then the state of the SON cells normalized. Functional activity of the PVN and PON decreased (the nucleolar volume of the neurosecretory cells diminished to 70--80%, the amount of the neurosecretory substance in the cells and the posterior lobe of the hypophysis was reduced). Such a decreased activity of the PVN and PON persisted till the end of the experiment. A positive correlation of the thyroid epithelium height and the nucleolar volume of the PVN and PON cells was established for both the PVN (r=0.81, P less than 0.05) and the PON (r=0.82; P less than 0.05); no significant correlation was revealed for the SON (r=0.51; P less than 0.05). Thus, functional similarity of the PVN and the PON, and some peculiarities in the SON reaction under conditions of the experiment described was demonstrated.

Animals↗

The distribution of pontine projection cells in visual and association cortex of the cat: an experimental study with horseradish peroxidase.

The projections from the visual and association areas of the cat's neocortex to the pons were investigated with horseradish peroxidase as retrograde tracer. Small injections were made into the pars basalis of the pons, along its entire rostrocaudal extent. The cortical areas considered were areas 17, 18, 19, 20, 21, and the lateral suprasylvian areas (LSA); the posterior (PMSA), and the anterior middle suprasylvian association area (AMSA), the anterior lateral association area (ALA) and the anterior suprasylvian association area (ASA). A pontine projection was found for all the areas investigated; however, areas differ in the relative strength of their projection, in their intraareal distribution of projection cells, and in the location of their projection zones within the pons. A low to moderate density of projection cells is seen in the areas 17, 18, 19, 20, 21, and in PMSA. The posterior part of LSA contains only a few projection cells, whereas in more anterior parts of LSA the density of projection cells is moderate to high. A relatively dense distribution of projection cells also appears in AMSA, ALA, and ASA. In those areas which are retinotopically organized (17, 18, 19, LSA) the representation of the center of gaze contains far fewer projection cells than the representation of peripheral vision. In the association areas the distribution of projection cells appears even. The projection zones from areas 17, 18, and 19 overlap with the zones from LSA in the anterior half of the basal pons. The projection zones from areas 20 and 21 and from ALA and ASA are located in the middle third and the projection zones from PMSA and AMSA spread throughout the entire rostrocaudal extent of the basal pons. Our findings indicate that efferent impulses from the visual cortical areas and from the association areas on the middle suprasylvian gyrus are relayed to the cerebellum exclusively via the basal pontine nuclei. The findings further suggest that the visual corticopontine projections carry a map of the visual field in which the cortical magnification factor is reduced.

Animals↗

Development of the precerebellar nuclei in the rat: IV. The anterior precerebellar extramural migratory stream and the nucleus reticularis tegmenti pontis and the basal pontine gray.

Sequential thymidine radiograms from rats injected on days E16, E17, E18, and E19 and killed 2 hours after injection and at daily intervals up to day E22 were used to establish the site of origin, migratory route, and settling patterns of neurons of the nucleus reticularis tegmenti pontis and basal pontine gray. The nucleus reticularis tegmenti pontis neurons, which are produced predominantly on days E15 and E16, derive from the primary precerebellar neuroepithelium. These cells, unlike those of the lateral reticular and external cuneate nuclei, take an anteroventral subpial route, forming the anterior precerebellar extramural migratory stream. This migratory stream reaches the anterior pole of the pons by day E18. In rats injected on day E16 and killed on day E18 some of the cells that reach the pons are unlabeled, indicating that they represent the early component of neurons generated on day E15. The cells labeled on day E16 begin to settle in the pons on day E19, 3 days after their production. These cells, migrating in an orderly temporal sequence, form a posterodorsal-to-anteroventral gradient in the nucleus reticularis tegmenti pontis. Unlike the neurons of all the other precerebellar nuclei, the basal pontine gray neurons derive from the secondary precerebellar neuroepithelium. The secondary precerebellar neuroepithelium forms on day E16 as an outgrowth of the primary precerebellar neuroepithelium, and it remains mitotically active through day E19, spanning the entire period of basal pontine gray neurogenesis. The secondary precerebellar neuroepithelium is surrounded by a horizontal layer of postmitotic cells, representing the head-waters of the anterior precerebellar extramural migratory stream. In rats injected on day E18 and killed on day E19 the cells are labeled in the proximal half of the stream around the medulla but those closer to the pons are unlabeled, indicating an orderly sequence of migration. In rats injected on day E18 and killed on day E20 the labeled cells reach the pole of the pons. In the basal pontine gray the sequentially generated neurons settle in a precise order. The neurons generated on day E16 form a small core posteriorly and the neurons generated on days E17, E18, and E19 form regular concentric rings around the core in an inside-out sequence.

Animals↗

Effects of short and long-lasting diabetes mellitus on mouse brain monoamines.

Concentrations of monoamines and their metabolites were investigated in various brain regions of 3, 50, and 100 days diabetic mice. An increase in the content of norepinephrine was observed in the pons-medulla and striatum in short-term (3 days) diabetic mice, and could be sustained for 100 days and 50 days, respectively. In the hypothalamus and cortex, the increase of norepinephrine was observed in both 50 and 100 day diabetic mice, but that of cerebellum was only observed in the 100 day diabetic mice. The concentration of dopamine was increased in the striatum both in short-term and long-term (50 and 100 days) diabetic mice, that of pons-medulla and cortex was increased in the long-term diabetic mice. Concentrations of the acidic metabolites of dopamine, dihydroxyphenylacetic acid and homovanillic acid were decreased in the hypothalamus, hippocampus and striatum, while increased in the pons-medulla and cortex. 5-Hydroxytryptamine concentration was increased in the hypothalamus, hippocampus, pons-medulla and cortex progressively from short-term to long-term diabetic mice. However, the concentration of its acidic metabolite, 5-hydroxyindoleacetic acid, was decreased in the hypothalamus, hippocampus, striatum, pons-medulla and cortex. These data suggest that diabetes is associated with a significant disturbance of brain monoamine metabolism. This disturbance was not generalized but related to some specific areas of the brain and some of these alterations were progressive from short term to long term diabetes.

Animals↗

Trigeminal projections to the peribrachial region in the muskrat.

The anterograde and retrograde transport of wheat germ agglutinin-horseradish peroxidase was used to study the trigeminoperibrachial pathway in the muskrat after injections of tracer into either the medullary dorsal horn or the dorsolateral pons. After injections into the medullary dorsal horn, labeled fibers ascended into the ipsilateral dorsolateral pons via the spinal trigeminal tract, within the neuropil of the trigeminal sensory complex and within the reticular formation adjacent to the spinal trigeminal nucleus. At caudal levels of the ipsilateral peribrachial area, dense terminal-like label distributed in the Kölliker-Fuse nucleus continued into the lateral parabrachial nucleus. At intermediate levels ipsilaterally, the Kölliker-Fuse nucleus again was labeled densely, as were areas analogous to the external lateral and external medial subnuclei of the parabrachial nucleus in the rat. A thin band of label along the ventral spinocerebellar tract outlined an unlabeled area in the central portion of the lateral parabrachial nucleus. Rostrally near the pontomesencephalic junction, the area designated the superior lateral subnucleus in the hamster was labeled, while sparser label was present more dorsally. Contralateral to the injections, caudal and intermediate levels of the peribrachial area contained only scant reaction product. However, the rostral area of the superior lateral subnucleus was labeled densely via fibers ascending in the trigeminothalamic tract. Injections made just rostral to the obex and either centered in or including the dorsal or ventral paratrigeminal nuclei produced similar labeling at caudal and intermediate levels of the peribrachial area. An exception, however, was that the caudal medial parabrachial nucleus was also labeled after the dorsal paratrigeminal injection. Also, only scant label was found in the rostral third of the dorsolateral pons on either side after these injections. Both trigeminothalamic and trigeminolemniscal pathways were labeled contralaterally after these injections. These trigeminal projections to the dorsolateral pons were compared to the projections from the nucleus tractus solitarii and the ventrolateral medulla. Numerous trigeminal neurons were labeled retrogradely after injections of wheat germ agglutinin-horseradish peroxidase into the dorsolateral pons. In the medullary dorsal horn, they were found almost exclusively in laminae I and V. Labeled neurons in lamina I were especially prominent in rostral ventral levels of the medullary dorsal horn. Labeled cells in lamina I were continuous with others found in the displaced band of substantia gelatinosa at the interface of the subnucleus caudalis and subnucleus interpolaris, as well as with those found in the ventral and dorsal paratrigeminal nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Respiration-related afferents to parabrachial pontine regions.

The dorsolateral pons around the parabrachial nucleus is an important participant in respiratory control. This area involves various respiration-related neurons, and their respiratory modulation is thought to arise from afferents from medullary respiratory neurons. Today, however, only a limited number of afferent sources have been identified. First, relatively well-characterized afferents to the pons are those originating from two types of the lung stretch receptors, slowly adapting and rapidly adapting receptors. That is, the majority of the second-order relay neurons of these receptors in the nucleus tractus solitarii project to the pons. Second, certain types of respiratory neurons of the medullary respiratory groups are either known to or presumed to project to the pons. For instance, major inhibitory neurons of the Botzinger complex, augmenting and decrementing expiratory neurons, send afferents to the pons. This article overviews such afferents and discusses their connectivity with pontine neurons.

Afferent Pathways↗

Effects of feeding grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of laying hens, turkey poults, and broiler breeder hens.

Three experiments were conducted to compare the effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of laying hens, turkey poults, and broiler breeder hens. In Experiment 1, thirty-six 45-wk-old laying hens were fed diets including the following for 4 wk: 1) control, 2) contaminated grains, and 3) contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent (GMA). Concentrations of brain neurotransmitters and metabolites were analyzed in pons, hypothalamus, and cortex by HPLC with electrochemical detection. Neurotransmitters and the metabolites measured included dopamine, 3,4-dihydroxylphenyacetic acid, homovanillic acid, serotonin [5-hydroxytryptamine (5-HT)], 5-hydroxyindolacetic acid, epinephrine, and norepinephrine. The feeding of contaminated grains significantly increased concentrations of 5-HT and decreased the 5-hydroxyindolacetic acid:5-HT in the pons region in the brain stem. Dietary supplementation with GMA prevented these effects. There was no effect of diet on concentrations of other neurotransmitters or metabolites in the pons, hypothalamus, or cortex. In Experiment 2, thirty-six 1-d-old turkey poults were fed diets including the following for 4 wk: 1) control, 2) contaminated grains, and 3) contaminated grains + 0.2% GMA. Hypothalamic, pons, and cortex neurotransmitter concentrations were not affected by diet. In Experiment 3, forty-two 26-wk-old broiler breeder hens were fed diets including the following for 15 wk: 1) control, 2) contaminated grains, and 3) contaminated grains + 0.2% GMA. There was no effect of diet on neurotransmitter concentrations in the pons, hypothalamus, or cortex. It was concluded that differences in intraspecies effects of these mycotoxins on brain neurotransmitter concentrations might explain the intraspecies differences in the severity of Fusarium mycotoxin-induced reductions in feed intake.

Animal Feed↗

Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis.

OBJECTIVE: Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. MATERIALS AND METHODS: Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative 18FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. RESULTS: The pons showed the best preservation of glucose metabolism in AD. Other reference regions showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. CONCLUSION: Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging.

Aged↗

The effects of reversible inactivation of the red nucleus on learning-related and auditory-evoked unit activity in the pontine nuclei of classically conditioned rabbits.

The pontine nuclei carry auditory conditioned stimulus information to the cerebellum during classical conditioning of the nictitating membrane response in rabbits. In well-trained animals learning-related as well as stimulus-evoked unit activity can be recorded throughout the pontine nuclei but particularly in the lateral and dorsolateral pons. Recent work in our laboratory has provided evidence that the learning-related unit activity in the pons is dependent on the interpositus nucleus and that the pons is not a site of essential plasticity for the learned response. In the present study we considered the question of whether learning-related unit activity might be projected from the interpositus nucleus to the pons through the red nucleus, a primary output target of the interpositus and a structure known to be essential for expression of the learned response. Multiple unit recordings were taken from lateral and dorsolateral pontine locations in well-trained rabbits before and during cooling of the red nucleus. Analysis of pooled data for all recording locations within the lateral and dorsolateral pons indicated that reversible inactivation of red nucleus abolished both stimulus-evoked and learning-related unit activity. However, we also found discrete recording locations where stimulus-evoked and learning-related unit activity were attenuated but not abolished by red nucleus cooling.

Animals↗

Regional distribution of the anticonvulsant and behavioural effects of bicuculline injected into the pontine reticular formation of rats.

Previous experimental work has established that activation of sites in the dorsal midbrain can suppress tonic hindlimb extension in the electroshock model of epilepsy. The most sensitive region for this effect is centred on the intercollicular area and is referred to as the dorsal midbrain anticonvulsant zone (DMAZ). Subsequent experiments have shown that the ipsilateral descending projection from this region to the ventrolateral pons is critically involved in mediating its tonic seizure-suppressing properties. The purpose of the present investigation was to test whether direct anticonvulsant effects in the electroshock model could be obtained from selective manipulation of DMAZ target regions in the ventrolateral pons. Animals were prepared with chronically implanted guide cannulae through which microinjections could be made directly into the lateral pontine reticular formation. Animals received injections of saline or bicuculline (25-100 pmol) administered either bilaterally or unilaterally. The effects of these injections on the animals' behaviour were determined in an open arena, after which maximal electroshock (1 s, 40 mA, 50 Hz AC) was administered via ear-clip electrodes and the duration of tonic hindlimb extension was recorded. Bilateral injections of bicuculline (100 pmol) suppressed tonic seizures at a significantly higher proportion of sites centred on DMAZ target regions of the ventrolateral pons than surrounding areas. For injections centred on this region the suppressive effects of bicuculline were dose-related in the range 25-100 pmol. Unilateral injections of bicuculline into the ventrolateral pons also effectively suppressed tonic seizures in the electroshock model. Within the ventral pons there was a significant association between the behavioural and anticonvulsant effects of bicuculline; injections suppressing tonic seizures were associated with the induction of fast continuous locomotor activity. These data confirm that the DMAZ recipient region of the ventrolateral pontine reticular formation is part of a circuit which can suppress the manifestation of tonic hindlimb extension in the electroshock model. Whether this property is related to the participation of this region in normal locomotion and posture remains to be determined.

Animals↗

Estradiol increases prolactin synthesis and prolactin messenger ribonucleic acid in selected brain regions in the hypophysectomized female rat.

Immunoreactive PRL which is not of pituitary origin, has been identified in many regions of the rat brain. We have previously demonstrated that estradiol increases hypothalamic immunoreactive PRL content in hypophysectomized female rats. To determine if estradiol stimulates PRL synthesis, we examined the effect of estradiol on the in vivo production of PRL, and on the expression of PRL messenger RNA (mRNA) in the hypothalamus, pons, and cerebral cortex. To examine the effect of estradiol on the in vivo production of PRL, [35S] methionine was injected into the lateral ventricle and its incorporation into immunoprecipitable PRL was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In estradiol, but not vehicle-treated hypophysectomized rats, a 24,000 M(r) immunoprecipitable PRL protein was detected in the hypothalamus and pons-medulla, 2 and 4 h after methionine administration. No immunoprecipitable PRL proteins were detected in the amygdala, hippocampus, cortex, or serum at either time point. In addition, in the hypothalamus, but not the pons-medulla, a second PRL band was detected with an apparent mol wt of 16,000K. To determine if estradiol increased the expression of PRL mRNA, copy DNA was obtained by reverse transcription of poly(A+) mRNA prepared from intact and vehicle or estradiol-treated hypophysectomized rats and analyzed by polymerase chain reaction amplification. In tissues from hypophysectomized rats, there was little, or no, detectable levels of PRL mRNA. In contrast, in estradiol-treated hypophysectomized rats PRL mRNA was easily detected in the hypothalamus and pons-medulla by polymerase chain reaction amplification. These data suggest that estradiol increases the PRL content in the hypothalamus and pons-medulla by increasing PRL gene expression, in a manner similar to that reported in the pituitary.

Animals↗