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H Baker

Publications and source records attributed to H Baker.

At least 91 records · Page 5Linked to original sources
PubMed1995

Olfactory marker protein mRNA is found in axons of olfactory receptor neurons.

The separation between the cell bodies of olfactory receptor neurons in the nasal cavity and their axon terminals in the olfactory bulb make them attractive for studying axonal transport. Although high molecular weight RNAs are generally believed to be excluded from axons of mature neurons, we demonstrate here that mRNA for olfactory marker protein (OMP), an abundant cytoplasmic protein selectively expressed in mature receptor cells, is present in rodent olfactory receptor axons. OMP RNA was detected by in situ hybridization at the light microscope level in axons and in terminals. By nuclease protection, the level of OMP RNA in the olfactory bulb was 5-10% of that in the olfactory epithelium where the cell bodies reside. In contrast to axonally transported vasopressin and oxytocin mRNAs, which are deficient in their 3' polyA tails, axonal OMP RNA fractionated as polyA+. OMP RNA was lost from axons and terminals after deafferentation, suggesting that OMP RNA was synthesized in receptor cell bodies in the epithelium and was transported into axons and terminals in the olfactory bulb. RNA for G(olf), a G-protein highly expressed in dendrites of mature olfactory receptor neurons, was not detected in the olfactory bulb. We hypothesize that the immature nature of the cytoskeleton and, specifically, the lack of tightly bundled microtubules allows transport of particular mRNAs in olfactory receptor axons.

Afferent Pathways↗
PubMed1995

The potassium channel subunit KV3.1b is localized to somatic and axonal membranes of specific populations of CNS neurons.

Potassium channels play major roles in the regulation of many aspects of neuronal excitability. These channels are particularly well suited for such multiplicity of roles since there is a large diversity of channel types. This diversity contributes to the ability of specific neurons (and possibly different regions of the same neuron) to respond uniquely to a given input. Neuronal integration depends on the local response of spatially segregated inputs to the cell and the communication of these integration centers with the axon. Therefore, the functional implications of a given set of K+ channels varies depending on their precise location on the neuronal surface. Site-specific antibodies were utilized to characterize the distribution of KV3.1b, a subunit of voltage-gated K+ channels in CNS neurons. KV3.1b subunits are expressed in specific neuronal populations of the rat brain, such as cerebellar granule cells, projecting neurons of deep cerebellar nuclei, the substantia nigra pars-reticulata, the globus pallidus, and the ventral thalamus (reticular thalamic nucleus, ventral lateral geniculate and zona incerta). The KV3.1b protein is also present in various neuronal populations involved in the processing of auditory signals, including the inferior colliculus, the nuclei of the lateral lemniscus, the superior olive, and some parts of the cochlear nuclei; as well as in several other neuronal groups in the brainstem (e.g., in the oculomotor nucleus, the pontine nuclei, the reticulotegmental nucleus of the pons, trigeminal and vestibular nuclei, and the reticular formation) and subsets of neurons in the neocortex, the hippocampus and the caudate-putamen shown by double staining to correspond to neurons containing parvalbumin. KV3.1b subunits are localized predominantly in somatic and axonal membranes (particularly in axonal terminal fields) but are much less prominent in dendritic arborizations. This distribution is different than that of other subunits of voltage gated K+ channels and is consistent with a role in the modulation of action potentials. KV3.1b proteins have a cellular and subcellular distribution different than the related KV3.2 subunits which express in Xenopus oocytes currents similar to those expressed by KV3.1b.

Amino Acid Sequence↗
PubMed1994

Distribution of the alpha-ketoglutarate dehydrogenase complex in rat brain.

The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a key enzyme in mitochondrial oxidation that appears critical to neurodegenerative diseases. Its activity in the brain declines in thiamine-deficient animals, Alzheimer's disease, and Wernicke-Korsakoff syndrome. Since selective cell populations are affected in these disorders, understanding the cellular distribution of KGDHC is important in order to define its role in the pathophysiology of these diseases. We used antisera against both bovine KGDHC and its E1k component to determine the immunocytochemical distribution of the enzyme and compare it with that of another mitochondrial enzyme, pyruvate dehydrogenase complex (PDHC) and a cholinergic neuronal marker, choline acetyltransferase (ChAT) in rat brain. Although low levels of immunoreactivity occurred in neurons, glia, and neuropil throughout the brain, some regions displayed relatively high perikaryal KGDHC enrichment. In the cerebral cortex, high immunoreactivity occurred mostly in layers III, V, and VI. The hippocampal pyramidal layer in CA1 and CA2 exhibited more intense staining than CA3. In the mammillary body, intensely labeled cells occurred in the supramammillary and lateral nuclei, while moderately stained cells predominated in the medial nucleus. The basal forebrain, basal ganglia, reticular and midline thalamic nuclei, red nucleus, pons, cranial nerve nuclei, inferior and superior colliculi, and cerebellar nuclei also contained highly immunoreactive neurons. The distribution of KGDHC overlapped with that of PDHC and colocalized to a limited extent with ChAT. These data are the first to demonstrate KGDHC immunoreactivity in discrete areas of rat brain and are vital to our understanding of selective vulnerability to metabolic insults and disease.

Animals↗
PubMed1994

Selective enrichment of cholinergic neurons with the alpha-ketoglutarate dehydrogenase complex in rat brain.

Numerous reports suggest a close interaction between acetylcholine homeostasis and oxidative metabolism. However, the neuroanatomical basis of this relationship has not been established. A previous study showed that a key mitochondrial enzyme, alpha-ketoglutarate dehydrogenase complex (KGDHC) occurs at low levels in neurons, glia and neuropil throughout the rat brain. Some regions including those that are enriched with a cholinergic neuronal marker, choline acetyltransferase (ChAT) show relatively high perikaryal enrichment of KGDHC. The current study utilized double label immunofluorescence to determine whether cholinergic neurons are enriched with KGDHC in rat brain. In cranial nerve nuclei, trapezoid nucleus, nucleus ambiguous and inferior olive, virtually all cholinergic neurons were enriched with KGDHC. However, in basal forebrain nuclei, only a subpopulation of cholinergic cells were intensely immunoreactive for KGDHC. These data provide morphological evidence to support the hypothesized link between cholinergic function and oxidative metabolism in specific brain regions.

Acetylcholine↗
PubMed1994

Gene expression in central cholinergic neurons in response to axotomy and deafferentation.

Although the molecular and cellular responses to injury in the central nervous system (CNS) have been widely investigated, few studies have examined the potential variations between direct and indirect neuronal injury. To differentiate between the response to axotomy and deafferentation, two central cholinergic populations were analyzed: the horizontal limb of the diagonal band of Broca (HLDB) and the interneurons in the corpus striatum (CS). At time points from one hour to eight weeks postinjury the levels of choline acetyltransferase (ChAT) mRNA and protein were assessed by in situ hybridization and immunohistochemistry. Also examined was the expression of the immediate early gene product, c-fos. One week post axotomy, neurons in the HLDB exhibited an increase in the levels of ChAT mRNA without a concomitant increase in ChAT protein, followed by a steady decrease reaching a nadir in both parameters at eight weeks. In contrast, a transient increase occurred at one week postdeafferentation in the levels of both ChAT mRNA and protein in the interneurons of the CS. Axotomized neurons in the HLDB did not exhibit either c-fos mRNA or protein expression, while robust fos induction occurred after one hour in deafferented neurons in the CS. These data demonstrate that the molecular and cellular responses differ following direct and indirect neuronal injury. Furthermore, they suggest that in these central cholinergic populations deafferentation may result in cellular hyperactivity and cell survival while axotomy results in decreased cellular activity and subsequent cellular regression.

Animals↗
PubMed1994

Early induction of rat brain tryptophan hydroxylase (TPH) mRNA following parachlorophenylalanine (PCPA) treatment.

Tryptophan hydroxylase (TPH) is the first and presumably rate-limiting enzyme in serotonin (5-HT) biosynthesis. End-product inhibition of rate-limiting enzymes is common and 5-HT is known to inhibit TPH activity in vivo. However, it is not known whether levels of 5-HT could also be involved in the regulation of the TPH gene. In order to determine whether TPH gene regulation is dependent on the 5-HT concentration, 5-HT levels were reduced by the administration of parachlorophenylalanine (PCPA). PCPA is a potent, specific and irreversible inhibitor of TPH activity which drastically reduces 5-HT concentration in the 5-HT neurons and terminals. When PCPA was administered, TPH activity in both cell bodies and nerve terminal areas, was reduced to 10% of control values and recovered to the control levels by day 7 in raphe nucleus, and within 14 days in the hypothalamus. In serotonergic terminal areas, 5-HT could not be detected immunohistochemically at day 1, but slowly recovered within 2 weeks. At all time points examined, aromatic L-amino acid decarboxylase (AADC) levels were not changed either in the cell body or terminal areas. The steady state levels of TPH mRNA estimated by in situ hybridization increased at day 1 and returned to control levels by day 4. AADC message levels were not altered throughout the periods. These data suggest that a decrease in 5-HT concentration may lead to an up-regulation of TPH gene transcription, by an, as yet, unknown mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Drastic and selective hyperinnervation of central serotonergic neurons in a lethal neurodevelopmental mouse mutant, Anorexia (anx).

The autosomal recessive lethal anorexia mutation in mice (anx/anx) causes starvation in preweanlings. In addition, this murine neurodevelopmental mutant shows other distinct phenotypic characteristics and dysfunctional behaviors. Previous studies strongly suggested that the mutation results in elevated serotonergic stimulation, because these traits are characteristic of such overstimulation and because brain serotonin is believed to have an inhibitory effect on feeding behavior. In this report, we show extensive serotonergic hyperinnervation in normal target fields (hippocampus, cortex, olfactory bulb and cerebellum) of mutant mice. Despite the extensive hyperinnervation, the normal laminar organization of the brain was retained. The specificity of the mutation to the serotonergic system was confirmed by demonstration of normal catecholaminergic innervation in the central nervous system (CNS), and this specificity was especially striking in a common target field, the cerebellum. Serotonergic hyperinnervation in these mutant preweanling mice may represent the underlying etiology of increased serotonergic stimulation which leads to anorexic starvation, abnormal behavior, and premature death.

Animals↗
PubMed1994

Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people.

A placebo-controlled double-blind trial of the effects of daily micronutrient supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skin test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned to placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12 mo of micronutrient ingestion. For the micronutrient group, there were statistically significant increases at 6 and/or 12 mo in the mean serum concentrations of ascorbate, beta-carotene, folate, vitamin B-6, and alpha-tocopherol. There was a significant increase at 12 mo in the number of subjects in the placebo group with one or more low concentrations. DHST responses to a panel of seven recall antigens were significantly increased at 12 mo in the micronutrient group but not the placebo group. This study demonstrates that daily supplementation with low-to-moderate doses of micronutrients can prevent low concentrations of some micronutrients and can improve DHST responses in healthy, independently living older adults.

Aged↗
PubMed1994

Biocidal action of chlorhexidine is annulled by nicotinic acid.

An analytical system comprising a bacterium and a protozoan was used to pinpoint the metabolic lesion whereby chlorhexidine (CLX) produced cell death. Nicotinic acid but not nicotinamide annulled the biocidal action of CLX. The results suggest that CLX may not permit bioconversion of nicotinamide to nicotinic acid to annul the growth inhibition induced by CLX.

Animals↗
PubMed1994

Differential expression of Shaw-related K+ channels in the rat central nervous system.

The family of mammalian genes related to the Drosophila Shaker gene, consisting of four subfamilies, is thought to encode subunits of tetrameric voltage-gated K+ channels. There is compelling evidence that subunits of the same subfamily, but not of different subfamilies, form heteromultimeric channels in vitro, and thus, each gene subfamily is postulated to encode components of an independent channel system. In order to identify cells with native channels containing subunits of one of these subfamilies (Shaw-related or ShIII), the cellular distribution of ShIII transcripts was examined by Northern blot analysis and in situ hybridization. Three of four ShIII genes (KV3.1, KV3.2, and KV3.3) are expressed mainly in the CNS. KV3.4 transcripts are also present in the CNS but are more abundant in skeletal muscle. In situ hybridization studies in the CNS reveal discrete and specific neuronal populations that prominently express ShIII mRNAs, both in projecting and in local circuit neurons. In the cerebral cortex, hippocampus, and caudate-putamen, subsets of neurons can be distinguished by the expression of specific ShIII mRNAs. Each ShIII gene exhibits a unique pattern of expression; however, many neuronal populations expressing KV3.1 transcripts also express KV3.3 mRNAs. Furthermore, KV3.4 transcripts are present, albeit at lower levels, in several of the neuronal populations that also express KV3.1 and/or KV3.3 mRNAs, revealing a high potential for heteromultimer formation between the products of three of the four genes. Expression of ShIII cRNAs in Xenopus oocytes was used to explore the functional consequences of heteromultimer formation between ShIII subunits. Small amounts of KV3.4 cRNA, which expresses small, fast-inactivating currents when injected alone, produced fast-inactivating currents that are severalfold larger when coinjected with an excess of KV3.1 or KV3.3 cRNA. This amplification is due to both an increase in single-channel conductance in the heteromultimeric channels and the observation that less than four, perhaps even a single KV3.4 subunit is sufficient to impart fast-inactivating properties to the channel. The oocyte experiments indicate that the apparently limited, low-level expression of KV3.4 in the CNS is potentially significant. The anatomical studies suggest that heteromultimer formation between ShIII proteins might be a common feature in the CNS. Moreover, the possibility that the subunit composition of heteromultimers varies in different neurons should be considered, since the ratios of overlapping signals change from one neuronal population to another. In order to proceed with functional analysis of native ShIII channels, it is important to known which subunit compositions might occur in vivo. The studies presented here provide important clues for the identification of native homo- and heteromultimeric ShIII channels in neurons.

Animals↗
PubMed1994

Vitamin activities in human portal, hepatic and femoral blood after vitamin ingestion.

The dynamics of intestinal absorption, blood concentration and distribution of thiamin, biotin, nicotinate, riboflavin, pantothenate, various folates (folic acid, folinic acid, pteroyltriglutamate), vitamins A, E, C, B12, and B6 were monitored in 12 patients by multiple simultaneous sampling of blood obtained by combined catheterization of portal vein, hepatic vein, and femoral artery after vitamin ingestion. All water-soluble vitamins proved elevated after vitamin ingestion principally in portal blood within 10 minutes as compared with hepatic and femoral blood. Elevated vitamin levels in portal blood--compared to hepatic and femoral blood--remained high even after 120 min. indicating that absorption from the gut was still progressing. In contrast, ingestion of the fat-soluble vitamins A and E evoked no elevated vitamin activity in portal blood. Within 10 min. after vitamin ingestion, all folates were converted into reduced and methylated 5-methyltetrahydrofolate (5-CH3THF) on passage through the gut. At this time, portal blood elevation of 5-CH3THF persisted before its elevation in hepatic or femoral blood. Presumably, the elevation was not due to the flushing of stored 5-CH5THF from tissues but rather of folate conversion to 5-CH3THF upon gut passage. The significance of these findings is discussed.

Administration, Oral↗
PubMed1993

Immunohistochemical analyses of the human olfactory bulb.

These studies explore the distribution of putative neuroactive peptides in the human olfactory bulb. Localization of synaptophysin-, serotonin-, cholecystokinin-, substance P-, and somatostatin-like staining was examined by immunocytochemical protocols. The results provide new insights into the composition and laminar segregation of subpopulations of neurons and neuronal processes in the human olfactory bulb. The prominent synaptophysin-like immunoreactivity observed in the glomeruli of the human olfactory bulb is consistent with the notion that the density of synapses, and hence the density of synaptic vesicles, is highest in the glomeruli. Serotonin-like immunoreactivity suggested a variable innervation of glomeruli ranging from a dense tangled ball of fibers within the glomerulus to a sparse innervation by a single immunoreactive fiber. There was no evidence of serotonin-like immunoreactive cell bodies in either the olfactory bulb proper, anterior olfactory nucleus, or proximal regions of the lateral olfactory tract. Cholecystokinin-like immunoreactivity was limited to fibers found largely in the juxtaglomerular region of the glomerular layer. In the deeper layers of the olfactory bulb, cholecystokinin-like immunoreactive fibers did not show any of branching or arborization that was evident in the juxtaglomerular region. Substance P-like immunoreactivity was seen in varicose fibers distributed in all of the human olfactory bulb laminae. In addition, stained multipolar neurons were found in the area of the anterior olfactory nucleus. Somatostatin-like immunoreactivity was similar to that of substance P in that a plexus of stained fibers was found in all laminae of the olfactory bulb. Also, somatostatin-like immunoreactive cell bodies were found in the area of the anterior olfactory nucleus. However, as compared to substance P, somatostatin had a less dense plexus of immunoreactive fibers in the olfactory bulb. These results increase our understanding of the fundamental organization of the human olfactory system. The current data, coupled with prior studies, provide a foundation from which to study the cellular pathology of diseases with known olfactory system sequelae such as Alzheimer's, Parkinson's, and schizophrenia.

Adult↗