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Chronic ethanol treatment increases expression of inhibitory G-proteins and reduces adenylylcyclase activity in the central nervous system of two lines of ethanol-sensitive mice.

The possibility that a 7-day period of ethanol exposure could regulate expression of specific GTP-binding regulatory proteins was investigated in two distinct brain regions from two different lines of ethanol-sensitive mice. Following ethanol treatment, plasma membranes were prepared from cerebellum and pons of short and long sleep mice. Studies of membranes were performed to assess hormone-sensitive adenylylcyclase activity and to quantify expression of G-protein subunits. Immunoblot analysis showed that levels of Gi alpha(1) and Gi alpha(2) were markedly increased in cerebellar and pons membranes from ethanol-exposed mice compared to controls. Treatment of short sleep mice with ethanol enhanced ADP-ribosylation of both a 41- and a 39-40 kDa protein catalyzed by pertussis toxin. Ethanol did not alter expression of Gs alpha as assessed by immunoblot analysis, cholera toxin-dependent ADP-ribosylation, or by the ability of detergent extracted Gs alpha to reconstitute a functional adenylylcyclase in membranes from S49 cyc- murine lymphoma cells, a cell line which genetically lacks Gs alpha. Moreover, ethanol exposure did not influence levels of G(o) alpha or G beta 35-36 in either cerebellar or pons membranes. Cerebellar and pons membranes from ethanol-exposed short sleep mice demonstrated significantly less adenylylcyclase activity following stimulation with GTP, GTP gamma S, AlF, forskolin, and stimulatory ligands for three distinct receptors which couple to Gs alpha. Pretreatment of membranes with pertussis toxin reversed the ethanol-induced inhibition in adenylylcyclase activity. These observations were not limited to one line of mice but were also documented in a second line of ethanol-sensitive mice (e.g. long sleep). We conclude that ethanol exposure enhances expression of Gi alpha(1) and Gi alpha(2) in ethanol-sensitive mice, and is associated with decreased adenylylcyclase activity. Enhanced expression of Gi alpha(1) and Gi alpha(2) may contribute to impaired signal transduction in the central nervous system, and reduce the efficacy of neurotransmitters which signal through the adenylylcyclase system.

Adenosine Diphosphate Ribose↗

[Changes of magnetization transfer ratio according to rat brain development].

We assessed the age-related changes in magnetization transfer ratio (MTR) value and the ratio of water content in rat brain (frontal lobe and pons) during normal development. All studies were done on 42 normal Wistar rats. MTR was calculated by using the equation (Moff-Mon)/Moff, where Moff and Mon were the measured signal intensities on the conventional and MT-prepared SPGR images, respectively. The ratios of water content were measured by comparing the wet weight with the dry weight of the frontal lobe and the pons, which were extracted from a rat brain soon after MTR measurements. The ratio of water content was calculated by using the equation 100 x (wet weight-dry weight)/wet weight (%). The ratio of water content decreased markedly during the first 30 days, but the decrease was very slight there after both in the frontal lobe and the pons. The change in MTR was similar to that of the ratio of water content, though the direction of change was opposite. Statistically significant inverse relationships existed between MTR and the ratio of water content both in the frontal lobe and the pons. MTR could be a new parameter with which to assess brain development.

Aging↗

Cardioexcitatory neurons in the snail Achatina fulica.

The excitatory motor unit of Achatina fulica is composed of five identified cardioregulatory motor neurons: three tonically active neurons (TAN-1, -2 and -3), a periodically oscillating neuron (PON) and a VG1 neuron. High frequency discharges in TAN neurons evoked slow depolarization waves. The PON elicited biphasic excitatory post synaptic potentials (EPSP). One spike in PON was sufficient to increase heart rate for several minutes. VG1 elicited discrete fast EPSP in the myocardium. Bursts of spikes from VG1 resulted in a summation of EPSP and transiently increased heart. VG1 inhibited spontaneous electrical activity in PON. Our results suggest that the use of semi-intact preparations allow elucidation of new functional cardioregulatory properties of intact neural networks.

Animals↗

Absence of magnetic resonance imaging evidence of pontine abnormality in infantile autism.

In vivo studies involving magnetic resonance imaging and studies of neuropathologic specimens have shown that autism is most consistently associated with developmental hypoplasia of the neocerebellum. We investigated whether the cerebellar hypoplasia was accompanied by gross structural abnormalities in the major input (cerebrocerebellar) and output (cerebrorubral) pathways to the cerebellum by measuring the area of the ventral pons (including the pontine nuclei and the transverse fibers) and the midbrain on midsagittal magnetic resonance images in 34 autistic and 44 subjects. The area of the entire pons and several regions of interest within the midbrain (including the superior and inferior colliculi) were also determined with midsagittal magnetic resonance images. We found no significant difference between measurements of the pons and midbrain in autistic and control subjects. Our data show no evidence of gross anatomic abnormalities in the input and output pathways to the cerebellum in autism, a finding that is consistent with previous studies of neuropathologic specimens; rather, the reduced size of the neocerebellum in autism appears to be the result of maldevelopment within the cerebellum itself.

Adolescent↗

Pontine ischemic rarefaction.

To investigate apparently asymptomatic, bilateral symmetrical predominantly pontine hyperintensities (PHI) on magnetic resonance imaging (MRI) scans in elderly patients, we examined the pons histopathologically in two brains of elderly hypertensives with PHI, and in three without PHI, on postmortem MRI scans. We also reviewed 85 serial in vivo MRI scans of patients over 60 and compared scan findings, vascular risk factors, and clinical symptoms between patients with PHI and a control group. A subcortical arteriosclerotic encephalopathy (SAE)-like pathology was present in the pons in only the two autopsy brains with PHI and corresponded with the location of PHI on the postmortem MRI scans and with the most frequent sites of PHI on in vivo scans. SAE also involved the hemispheric white matter in one of the autopsy brains. Five of 16 (31%) patients with, and 4 of 69 (6%) without, PHI on in vivo MRI scans had marked periventricular hyperintensity (PVHI) compatible with SAE (p = 0.01). We conclude that an SAE-like pathology may be seen in the pons in elderly hypertensives and this pathology is probably the cause of PHI seen on MRI scans of patients over 60 years of age.

Aged↗

Focal projections of cat auditory cortex to the pontine nuclei.

The pontine nuclei (PN) receive projections from the auditory cortex (AC) and they are a major source of mossy fibers to the cerebellum. However, they have not been studied in detail using sensitive neuroanatomical tracers, and whether all AC areas contribute to the corticopontine (CP) system is unknown. We characterized the projection patterns of 11 AC areas with WGA-HRP. We also compared them with their corticothalamic and corticocollicular counterparts. A third objective was to analyze the structure of the CP axons and their terminals with BDA. Both tracers confirm that all AC areas projected to lateral, central, and medial ipsilateral pontine divisions. The strongest CP projections were from nontonotopic and polymodal association areas. Preterminal fibers formed single terminal fields having many boutons en passant as well as terminal endings, and there was a specific morphological pattern for each pontine target, irrespective of their areal origin. Thus, axons in the medial division had a simpler terminal architecture (type 1 terminal plexus); both the central and lateral pons received more complex endings (type 2 terminal plexus). Auditory CP topographical distribution resembled visual and somatosensory CP projections, which preserve retinotopy and somatotopy in the pons, respectively. However, the absence of pontine tonotopy suggests that the AC projection topography is unrelated to tonotopy. CP input to the medial and central pons coincides with the somatosensory and visual cortical inputs, respectively, and such overlap might subserve convergence in the cerebellum. In contrast, lateral pontine input may be exclusively auditory.

Animals↗

The pontocerebellar system in the rat: an HRP study. II. Hemispheral components.

The projection of basilar pontine neurons to the cerebellar hemispheres was studied to pigmented rats by means of the retrograde transport of horseradish peroxidase. Injections of horseradish peroxidase were restricted to the lateral aspects of the lobulus simplex (11 cases), crus I (26 cases), crus II (23 cases), and paramedian lobule (18 cases). The main focus of labeled neurons following lobulus simplex injections of horseradish peroxidase was located in the ventral pons, at rostral levels. Interestingly, the majority of labeled cells were distributed ipsilateral to the injection site. After crus I injections, however, labeled neurons were most evident contralaterally , although labeled ipsilateral cells were conspicuous rostrally. The majority of labeled cells were characteristically distributed along the medial, ventral, and lateral perimeters of the pontine gray. This pattern of labeling contrasts with that in cases of crus II injections, in which the main focus of labeled somata occupied more central regions of medial and ventral portions of the pons. Similarly, the pattern of labeling following injections into the paramedian lobule largely avoided the medial and lateral perimeters of the pontine gray, while numerous labeled somata occupied the central region of the pons. In addition to the pontine regions described above, labeled cells were observed in various cases in the dorsal peduncular region, the lateral and dorsolateral areas, and the nuclear reticularis tegmenti pontis (NRTP) where three separate zones of labeling could be discerned in various cases. Several general organizational features were derived from these studies. Although specific quantitation procedures were not applied, the number of ipsilaterally labeled neurons was impressive in some cases, as was the mirror-image location of certain ipsi- and contralateral cell clusters. It was also noted that certain, similarly located clusters of labeled pontine neurons were present in cases in which injections were made into different cerebellar lobules, at least raising the possibility that some pontine neurons might give rise to divergent projections of multiple cerebellar locations, Moreover, it was evident that the location of certain clusters of labeled neurons was congruent with terminal zones of various pontine afferent systems, particularly those of the sensorimotor cortex. Combining the latter finding with the preceeding notion regarding pontocerebellar divergence suggests a mechanism by which sensorimotor information might be transmitted to several different cerebellar locations.

Afferent Pathways↗

Further observations on the cerebellar projections from the pontine nuclei and the nucleus reticularis tegmenti pontis in the rhesus monkey.

The projections from the pontine nuclei and the necleus reticularis tegmenti pontis (N.r.t.) onto the flocculus, uvula, and the paramedian lobule were studied with retrograde transport of horseradish peroxidase n the rhesus monkey. The main findings are as follows: There is a conspicuous tendency for labeled cells to occur in numerous discrete clusters in the pontine nuclei after injections of these parts of the cerebellum. There appears to be very limited overlap between pontine cell groups projecting to the flocculus, the uvula, and the paramedian lobule, respectively. The flocculus appears to receive a substantial projection from the pontine nuclei. The projection is almost totally crossed (3% ipsilateral), and arises mainly laterally in the rostral half of the pons but in addition from a minor group dorsomedially. The flocculus receives a bilateral projection (slight contralateral preponderance) from medial and dorsomedial parts of the NRT. The number of labeled cells in the NRT was 13% of the number in the pontine nuclei. the uvula is amply supplied from the pontine nuclei. The projection takes origin throughout the rostrocaudal extent of the pons, from one medial and one dorsolateral region. Labeled cells are found in greatest number dorsolaterally in the rostral half of the pons. In the caudal N.r.t., one medial and one lateral cell group were labeled after injection of the uvula. The number of labeled cells in the N.r.t. was only 4% of the number in the pontine nuclei. Findings with regard to the paramedian lobule confirm and extend earlier observations in the monkey (Brodal, '79, '80). The present results are discussed in relation to HRP studies of the pontocerebellar projection in lower animals. Several possible species differences are noted--for example, with regard to projections to the flocculus. There is some evidence that the pontocerebellar projection is more precisely organized in the monkey than in lower animals.

Animals↗

Distribution of galaninlike immunoreactivity in the rat central nervous system.

The localization of galanin (GAL) immunoreactive (IR) neuronal structures in the rat central nervous system has been investigated by using the indirect immunofluorescence technique. GAL-IR structures were seen in high concentrations in the hypothalamus, medulla oblongata, and spinal cord. Less extensive systems were detected in the telencephalon, thalamus, mesencephalon, and pons, while virtually no GAL-positive structures were seen in the olfactory bulb and cerebellum. Major populations of cell bodies staining for GAL-like material were seen in many areas. In the telencephalon somata were revealed in the bed nucleus of stria terminalis, in the nucleus of the diagonal band, medial septum, and in the medial aspects of the central amygdaloid nucleus, and in small numbers in cortical areas. The anterodorsal and periventricular nuclei of the thalamus contained positive cell bodies. In the hypothalamus GAL-IR somata were seen in the medial and lateral preoptic nuclei, arcuate nucleus, periventricular nucleus, in the dorsomedial nucleus, in the medial forebrain bundle area, in the tubular, caudal, accessory, supraoptic, and paraventricular magnocellular nuclei and lateral to the mammillary recess. The dorsal raphe nucleus hosted a large number of GAL-positive somata. Locus coeruleus of the pons contained a large number of GAL-IR perikarya. In the medulla oblongata positive somata were found in the caudal spinal trigeminal nucleus, the nucleus of the solitary tract, and in the ventral lateral area just rostral to area postrema. Small cell bodies were detected in the superficial layers of the dorsal horn of the spinal cord at all levels and in lamina X at lumbar levels. Analysis of GAL-positive fibers in the telencephalon revealed highly or medium-dense networks in the lateral septal nucleus, in the bed nucleus of stria terminalis, and in the central and medial amygdaloid nuclei. Positive fibers were found in the thalamus in and around the periventricular nucleus as well as in the lateral habenular nucleus and extending in a lateral, caudal direction from the third ventricle and fasciculus retroflexus to the lateral tip of the medial lemniscus. In the hypothalamus the external layer of the median eminence contained a very dense fiber network. Dense or medium-dense GAL-IR networks were detected in the periventricular nucleus, throughout the medial and lateral preoptic areas, in the medial forebrain bundle area, in the dorsomedial nucleus, and lateral to the mammillary recess. In the pons GAL-IR fibers were seen in the parabrachial nuclei, dorsal to the superior olive, and in the periaqueductal central gray.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Visual projections to the pontine nuclei in the rabbit: orthograde and retrograde tracing studies with WGA-HRP.

Visual projections to the pontine nuclei in the rabbit were examined by means of both orthograde and retrograde tracing of WGA-HRP. The tecto-pontine projection was examined following microinjections of WGA-HRP in the right superior colliculus. The projection to the pontine nuclei is strictly ipsilateral and terminates at middle and caudal levels of the pons. The projection is absent in rostral pontine nuclei. The strongest projection is to the dorsal border of the dorsolateral pontine nuclei and is the only projection seen when the primary injection site is confined to superficial laminae. When the primary injection site also includes intermediate and deep laminae, patches of labelled terminals are also seen within dorsolateral, lateral, peduncular, paramedian, and ventral pontine nuclei as well as in the contralateral nucleus reticularis tegmenti pontis. The striate corticopontine projection was also examined with orthograde tracing of WGA-HRP. The striate corticopontine projection is ipsilateral. Most labelled terminals were seen in dorsolateral and lateral pontine nuclei throughout the rostral half of pons with some additional terminal labelling in paramedian and peduncular nuclei. Labelled terminals were also seen in ventral pontine nuclei throughout the middle and caudal levels of the pons. In a retrograde tracing study, visual projections to the pontine nuclei were examined following microinjections of WGA-HRP into the pontine nuclei. Labelled cells were seen ipsilaterally in superficial and deep laminae of the superior colliculus and in layer V of striate and surrounding occipital cortex. The pontine nuclei also receive ipsilateral projections from the ventral lateral geniculate, the nucleus of the optic tract, anterior and posterior pretectal nuclei, and the dorsal and medial terminal nuclei of the accessory optic system. These pathways are potential sources of visual input to the cerebellum.

Animals↗

Projections to the basis pontis from the superior temporal sulcus and superior temporal region in the rhesus monkey.

The present investigation was designed to determine the origins in the temporal lobe, and terminations in the pons, of the temporopontine pathway. Injections of tritiated amino acids were placed in multimodal regions in the upper bank of the superior temporal sulcus (STS), and in unimodal visual, somatosensory, and auditory areas in different sectors of the lower bank of the STS, the superior temporal gyrus (STG), and the supratemporal plane (STP). The distribution of terminal label in the nuclei of the basis pontis was studied using the autoradiographic technique. Following injections of isotope into the multimodal areas (TPO and PGa) in the upper bank of the STS, intense aggregations of label were observed in the extreme dorsolateral, dorsolateral, and lateral nuclei of the pons, and modest amounts of label were seen in the peripeduncular nucleus. The caudalmost area TPO projected in addition to the ventral and intrapeduncular pontine nuclei. The second auditory area, AII, and the adjacent auditory association areas of the STG and STP contributed modest projections to the dorsolateral, lateral, and peripedunuclar nuclei, but generally spared the extreme dorsolateral nucleus. The lower bank of the STS, which subserves central vision, the somatosensory associated region at the fundus of the rostral STS, and the primary auditory area did not project to the pons. The higher order, multimodal STS contribution to the corticopontocerebellar circuit may provide a partial anatomical substrate for the hypothesis that the cerebellum contributes to the modulation of nonmotor functions.

Amino Acids↗

Single-voxel long TE 1H-MR spectroscopy of the normal brainstem and cerebellum.

PURPOSE: To evaluate the feasibility of single voxel 1H-MRS of the CNS structures contained in the posterior cranial fossa and to determine the distribution of the normal metabolite ratios, concentrations, and T2 relaxation times in the midbrain, pons, medulla, dentate nucleus and cerebellar vermis. MATERIALS AND METHODS: A total of 147 single voxel 1H-MR spectra with a point-resolved proton spectroscopy sequence (PRESS) sequence and echo time (TE) of 136 or 272 msec were obtained in the midbrain, pons, medulla, dentate, and vermis of 31 healthy volunteers. In seven additional patients; the concentrations and T2 relaxation times of metabolites were obtained in the same locations (except the medulla) with an external phantom calibration method and a four TE PRESS technique. RESULTS: Ten (27%) of 36 spectra acquired in the medulla were of poor quality. A similar ranking of the N-acetyl aspartate (NAA)/creatine (Cr) ratio and choline(Cho)/Cr ratios in the five locations for the two TEs was observed, with the highest values in the pons (mean NAA/Cr = 4.16 +/- 0.6 and Cho/Cr =2.66 +/- 0.6 at TE 272) and the lowest values in the dentate and vermis (mean NAA/Cr = 1.66 +/- 0.2 and Cho/Cr = 1.20 +/- 0.2 at TE 272). The analysis of variance showed significant regional differences of the NAA and Cr concentrations, which had the highest values in the dentate. Non-significant regional differences were observed for the concentration of Cho and for the T2 of the metabolites. CONCLUSION: With the exception of the medulla, single voxel 1H-MRS enables an in vivo biochemical analysis of the CNS structures contained in the posterior cranial fossa. Regional differences in the metabolite ratios and concentrations must be considered when employing 1H-MRS for evaluation of diseases of the brainstem and cerebellum.

Adult↗

Cortical atrophy in the cerebellar variant of multiple system atrophy: a voxel-based morphometry study.

This study aimed to determine in vivo the atrophy patterns in clinically established cerebellar variant of multiple-system atrophy (MSA-C) using voxel-based morphometry (VBM). Thirteen patients with MSA-C (12 probable, 1 possible) and 13 healthy controls matched for age and sex were included. High-resolution MR images were acquired with a 1.5 T scanner. Images were normalized onto a study-specific template, segmented into the tissue compartments, modulated with the Jacobian determinants, and finally smoothed with a Gaussian kernel filter of 10 mm. The general linear model was used to assess statistical differences in gray and white matter. Infratentorial atrophy was observed in the cerebellar hemispheres, vermis, mesencephalon, and pons of MSA-C patients. Supratentorial volume loss was found in orbitofrontal and mid-frontal regions as well as in temporomesial and insular areas of both hemispheres. A negative correlation was observed between a cerebellar ataxia score and the volume of cerebellar hemispheres, peduncles, and pons. To compare this atrophy pattern to that of spinocerebellar ataxia (SCA2), which was previously reported by our group, a conjunction analysis was assessed. We observed a volume loss shared by both disorders comprising the cerebellum, vermis, pons, mesencephalon, orbitofrontal, mid-frontal, and temporomesial cortex of both hemispheres as well as the left insular cortex.

Adult↗

Blink reflex in patients with an ischaemic lesion of the brain-stem verified by MRI.

The electrically elicited blink reflex was investigated in 25 patients with ischaemic lesions of the pons or the medulla oblongata. Only patients with a lesion on MRI appropriate to the clinical syndrome were included. Twenty patients had an infarction of the pons, bilateral in 5. Additional 5 patients had an infarction of the dorsolateral medulla oblongata. Patients with hemispheric lesions were excluded. Four of the 5 patients with Wallenberg's syndrome showed delayed R2 components to stimulation ipsilateral to the lesion. Additional loss of the ipsilateral R1 component was observed in 1 patient. Fifteen of the 20 patients with pontine infarctions had pathological blink reflexes. All 6 patients with a unilateral pons lesion and an abnormality of R1 had this abnormality on the side contralateral to the lesion. In 3 cases with bilateral pontine infarction R1 was abnormal on one side or on either side. Of 11 patients with a normal R1, 6 had isolated abnormalities of R2 without consistent correlation to the side of the lesion. We conclude that abnormalities of the blink reflex are of minor localizing value in pontine infarction. This may be explained by the fact that a pontine infarction affects either the reflex arch itself or descending pathways that have a modulating influence on the reflex arch. Infarctions of the medulla oblongata, however, have characteristic abnormalities that have already been described.

Adult↗

Gangliosides in various brain areas of three inbred strains of mice.

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p less than 0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri- and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.

Animals↗

Higher environmental temperature-induced change in synaptosomal acetylcholinesterase activity of brain regions.

Exposure of adult male albino rats to higher environmental temperature (HET) at 35 degrees for 2-12 hr or at 45 degrees for 1-2 hr increases hypothalamic synaptosomal acetylcholinesterase (AChE) activity. Synaptosomal AChE activity in cerebral cortex of rats exposed to 35 degrees for 12 hr and in cerebral cortex and pons-medulla of rats exposed to 45 degrees for 1-2 hr are also activated. AChE activity of synaptosomes prepared from normal rat brain regions incubated in-vitro at 39 degrees or 41 degrees for 0.5 hr increases significantly in cerebral cortex and hypothalamus. The activation of AChE in pons-medulla is also observed when this brain region is incubated at 41 degrees for 0.5 hr. Increase of (a) the duration of incubation at 41 degrees and (b) the incubation temperature to 43 degrees under in-vitro condition decreases the synaptosomal AChE activity. Lineweaver-Burk plots indicate that (a) in-vivo and in-vitro HET-induced increases of brain regional synaptosomal AChE activity are coupled with an increase of Vmax without any change in Km (b) very high temperature (43 degrees under in-vitro condition) causes a decrease in Vmax with an increase in Km of AChE activity irrespective of brain regions. Arrhenius plots show that there is a decrease in transition temperature in hypothalamus of rats exposed to either 35 degrees or 45 degrees; whereas such a decrease in transition temperature of the pons-medulla and cerebral cortex regions are observed only after exposure to 45 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

Changes in regional brain synaptosomal high affinity choline uptake during the development of hypertension in spontaneously hypertensive rats.

The high-affinity uptake of choline (HAChU) by freshly prepared crude synaptosomal fractions was employed as relative measure of regional brain cholinergic activity. The Vmax for uptake as determined by the accumulation of a tracer amount of 3H-choline in the presence of unlabeled choline (0.2-2 microM) varied 6 fold depending upon the region examined (stratum greater than hypothalamus greater than medulla-pons). HAChU was hemicholinium-3-sensitive and linear at 37 degrees C from 1 to 8 min in all brain regions. Respective brain synaptosomal fractions derived from adult (12 week old) spontaneously hypertensive (SH) rats and normotensive Wistar Kyoto (WK) rats revealed no difference in the Vmax for HAChU from synaptosomes derived from the striatum of either strain. However, there was a significant increase in the Vmax for HAChU measured from the medulla-pons of SH rats compared with WK rats. In older (22 weeks) rats, the Vmax for HAChU was 78% greater than age-matched WK control rats. In addition, a highly significant correlation was found between resting systolic blood pressure and the Vmax for HAChU both in the medulla-pons (r = 0.76) and hypothalamus (r = 0.48). That the increase in HAChU in SH rats was not a consequence of elevated pressure, was indicated by the lack of effect of prolonged i.v. infusion of pressor agents in normotensive rats on HAChU. These findings are consistent with a role for brain cholinergic neurons in the maintenance of hypertension in SH rats.

Animals↗

Effects of aging on the content, composition and synthesis of sphingomyelin in the central nervous system.

Sphingomyelin (SPH) content and composition in different regions of the brain were analyzed in 2.5, 21.5 and 26.5-month-old rats. SPH content increased in the cerebral hemispheres, cerebellum and medulla oblongata plus pons as age increased. The highest SPH content was observed in 26.5-month-old rats, with values increasing by 1.74, 2.75 and 0.88-fold, respectively, over 2.5-month-old rats. The SPH fatty acid composition of brains from aged rats was markedly different from that of adult rats. Between 2.5 and 26.5 months of age the monoenoic/saturated fatty acid ratio increased from 0.22, 0.30 and 0.54 to 0.54, 0.68 and 1.03 in cerebral hemispheres, cerebellum and medulla oblongata plus pons, respectively. The percentage and content of fatty acids longer than 22 carbon atoms esterified to SPH increased with age from 18, 26 and 44 to 48, 52 and 62 mole % in cerebral hemispheres, cerebellum and medulla oblongata plus pons in 26.5-month-old rats. In subcortical white matter from aged rats, monoenoic 22-26 carbon atom fatty acids increased more than the saturated ones in 21.5-month-old rats relative to 2.5-month-old rats. In vitro synthesis of SPH from [3H]choline and [3H]palmitic acid in cerebral cortex and cerebellum showed no significant differences between adult rats and those 21.5 months of age. In cerebellum and in cerebral cortex, [14C]serine incorporation increased in aged rats. The results suggest that aging induces increases in both SPH content and in the monoenoic/saturated fatty acid ratio. These increases are quantitatively different in all brain regions analyzed.

Aging↗