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PubMedDate not supplied

Noradrenergic abnormalities in the central nervous system of seizure-naive genetically epilepsy-prone rats.

Norepinephrine (NE) concentrations were measured in 15 discrete areas of the central nervous system of two types of genetically epilepsy-prone rats (GEPRs) and in nonepileptic controls. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had extensive abnormalities in brain NE concentration. Deficits of equal magnitude in GEPR-3s and GEPR-9s were found in the spinal cord, midbrain minus the inferior colliculus, inferior colliculus, hypothalamus, amygdala, hippocampus, occipital + parietal cortex, frontal cortex, and olfactory septum. Because both types of GEPRs share these deficits and share seizure susceptibility, we hypothesize that these areas are candidates for regulation of seizure susceptibility in GEPRs. In addition, because GEPR-9s have more severe seizures than GEPR-3s and because GEPR-9s had greater NE deficits in several brain areas (cerebellum, pons-medulla, thalamus, and possibly the temporal cortex and olfactory bulbs), we hypothesize that these areas may be important in regulation of seizure severity in GEPRs. All animals used in these experiments had been protected from seizure-provoking stimuli and were naive to seizures. Because the abnormalities in NE concentration were present in seizure-predisposed animals that were protected from seizures, we conclude that these abnormalities are important components of the seizure-predisposition characteristic of GEPRs and do not result from seizure experience.

Acoustic Stimulation↗
PubMed2001

Olfactory epithelium grafts in the cerebral cortex: an immunohistochemical analysis.

OBJECTIVE: To develop an alternative model for studying the regenerative capacity of olfactory neurons. STUDY DESIGN: An immunohistochemical analysis of mouse olfactory epithelium transplanted to the cerebral cortex. METHODS: Strips of olfactory epithelium removed from donor mice at postnatal day 5 to day 20 were inserted into the parietal cortex of adult mice. Recipient animals were allowed to survive for 25 to 120 days and then perfused with 4% paraformaldehyde 1 hour after bromodeoxyuridine injection. The brains were processed, and frozen sections were obtained. Sections through transplant tissue were analyzed using immunohistochemistry and compared with normal olfactory epithelium. RESULTS: Graft survival approached 85% with mature olfactory neurons detected in 35% of the transplants stained for olfactory marker protein. Transplant epithelium resembled normal olfactory epithelium containing mature olfactory neurons and axon bundles. CONCLUSIONS: Studies of olfactory neuron regeneration have been limited by the inability to produce cultures with long-term viability. Olfactory epithelial grafts to the cerebral cortex provide an alternative approach to the study of olfactory neuron regeneration.

Animals↗
PubMedDate not supplied

Comparative aspects of the olfactory portion of the entorhinal cortex and its projection to the hippocampus in rodents, nonhuman primates, and the human brain.

The entorhinal cortex is a component of the hippocampal formation characterized by its projection to the dentate gyrus. Cortical input is relayed to the hippocampus through the entorhinal cortex. The entorhinal cortex can be recognized best in mammals, and it reaches its maximal importance in both human and nonhuman primates. In primates, but not in rodents, the olfactory projection from the olfactory bulb is the only direct sensory projection reaching the entorhinal cortex, where it defines a rostromedial subfield (olfactory subfield of the entorhinal cortex, EO). In this communication, we consider some comparative aspects of this projection in rodents, nonhuman primates, and human brains, in relation to the forward projection to the hippocampus. We base our analysis on the following three considerations: (1) Topology: Topologically, the entorhinal cortex lies medial to the rhinal fissure, well developed in all mammals except in humans. EO maintains the same topological relationship to the rhinal fissure in the three mammalian orders. (2) Cytoarchitecture: The rostromedial portion shows poorer lamination compared with caudomedial portions of the entorhinal cortex in the three mammalian orders examined. (3) Connectivity: In rodents, the olfactory projection covers the whole extent of the entorhinal cortex, whereas it decreases substantially in macaques, where it roughly covers 15% of the entorhinal cortex. The human EO as defined by topological and cytoarchitectonic criteria may be even less than in macaques. Interestingly, good evidence exists that all of these mammalian orders maintain the same topographical scheme of projection to the rostral end of the hippocampus.

Animals↗
PubMed1977

Projections from the amygdaloid complex and adjacent olfactory structures to the entorhinal cortex and to the subiculum in the rat and cat.

Axonal projections are described from the lateral and basolateral nuclei of the amygdaloid complex, and from the overlying periamygdaloid and prepiriform cortices and the endopiriform nucleus, to the lateral entohinal area, the ventral part of the subiculum, and the parasubiculum in the cat and rat. All of these projections have well-defined laminar patterns of termination, which are complementary to those of other projections to the same structure. Based on these results, and on cytoarchitectonic distinctions, the lateral entohinal area has been divided into dorsal, ventral, and ventromedial subdivisions. The olfactory bulb and prepiriform cortex project to layers IA and IB, respectively, of all three subdivisions, but the lateral amygdaloid nucleus has a restricted projection to layer III of the ventral subdivision only. The periamygdaloid cortex projects to layer II of the ventromedial and adjoining parts of the ventral subdivisions. The ventral part of the subiculum receives fibers from the posterior division of the basolateral nucleus, which terminate in the cellular layer and the deep half to one-third of the plexiform layer. The periamygdaloid cortex and the endopiriform nucleus also project to the same part of the subiculum, but these fibers terminate in the outer part of the plexiform layer. None of these projections extend into the dorsal part of the subiculum. The posterior division of the basolateral nucleus also projects to the posterodorsal part of the parasubiculum ("parasubiculum a" of Blackstad, '56). These fibers end in the deeper part of the plexiform layer and the superficial part of the cellular layer.

Afferent Pathways↗
PubMed1984

Triiodothyronine receptors in adult rat brain: topographical distribution and effect of hypothyroidism.

The binding properties (affinity constant Ka and number of binding sites) of the nuclear receptors for triiodothyronine (T3) were studied in selected brain areas of the adult rat: cerebral cortex, cerebellum, olfactory bulb, caudate nucleus, hippocampus, hypothalamus and pituitary. Normal rats were compared to hypothyroid animals. The Ka of the nuclear receptors in the different parts of the brain had a similar order of magnitude (10(9) M-1) except for the hypothalamus where the value was lower (6 X 10(7) M-1). In hypothyroid animals, two main changes were observed in the properties of nuclear receptors: the Ka in the cerebral cortex was reduced by half, whereas in the pituitary the value was three times higher than in controls. In contrast to the decreased affinity, hypothyroidism enhanced the maximal binding capacity, especially in the cerebral cortex, the olfactory bulb, the caudate nucleus and the hippocampus. Of particular interest were the effects of hypothyroidism on the pituitary receptors which showed a markedly increased affinity for T3 and a reduced number of binding sites; this observation could be related to the control feedback mechanism of thyroid-stimulating hormone secretion by thyroid hormones.

Animals↗
PubMed1995

Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo sequences: preliminary results.

Autoradiographic studies have shown that low dose ketamine produces increases in regional glucose utilisation and blood flow in the hippocampus, cerebral cortex, and olfactory lobe in the rat brain, probably due to antagonism at the NMDA receptor. Functional MRI using deoxyhaemoglobin contrast can be used to study changes in regional cerebral blood flow (rCBF). Long TE gradient-echo sequences were used to study changes in rCBF produced by low dose ketamine in rats anaesthetised with nitrous oxide, supplemented with either halothane (HAL) or fentanyl/fluanisone/midazolam (FFM) combination. Images from rats in the FFM group showed a 10-14% increase in signal intensity in the hippocampus, cerebral cortex, and olfactory lobe following either a single bolus or a low dose infusion of ketamine (p < .05). These changes were significantly reduced in the HAL group (p < .005). Halothane is known to attenuate the changes in regional glucose utilisation produced by the noncompetitive NMDA antagonist dizocilpine (MK-801), and its effects on ketamine-induced changes in rCBF seen in this study may be due to a similar effect. The potential use of functional MRI in studying the effect of pharmacological interventions on rCBF is discussed.

Anesthetics, Dissociative↗
PubMed2000

Expression of ODC and its regulatory protein antizyme in the adult rat brain.

Ornithine decarboxylase and its inhibitor protein, antizyme are key regulators of polyamine biosynthesis. We examined their expression in the adult rat brain using in situ hybridization and immunocytochemistry. Both genes were widely expressed and their expression patterns were mostly overlapping and relatively similar. The levels of antizyme mRNA were always higher than those of ornithine decarboxylase mRNA. The highest expression for both genes was detected in the cerebellar cortex, hippocampus, hypothalamic paraventricular and supraoptic nuclei, locus coeruleus, olfactory bulb, piriform cortex and pontine nuclei. Ornithine decarboxylase and antizyme mRNAs appeared to be localized in the nerve cells. ODC antibody displayed mainly cytoplasmic staining in all brain areas. Antizyme antibody staining was mainly cytoplasmic in the most brain areas, although predominantly nuclear staining was detected in some areas, most notably in the cerebellar cortex, anterior olfactory nucleus and frontal cortex. Our study is the first detailed and comparative analysis of ornithine decarboxylase and antizyme expression in the adult mammalian brain.

Animals↗
PubMed2001

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region.

Aged↗
PubMed2005

Effects of radiotherapy on olfactory function.

BACKGROUND AND PURPOSE: Changes in olfactory function have been reported in patients receiving significant doses of radiation to the olfactory epithelium. Aim of this study was to investigate severity and time course of changes in olfactory function in patients irradiated for tumours of the head and neck region. MATERIAL AND METHODS: Forty-four patients receiving radiotherapy (RT) for tumours in the area of the head and neck participated (16 women, 28 men; age 11-81 y; mean 55 y). Olfactory function was measured before and bi-weekly during RT for 6 weeks. A subgroup (25 patients) was followed for 12 months. Patients were divided into two groups according to the dose to the olfactory epithelium. Twenty-two patients ('OLF group') had radiation doses to the olfactory epithelium between 23.7 and 79.5 Gy (median 62.2 Gy). In the 22 patients of the 'non-OLF group' the dose applied to the olfactory epithelium was significantly lower (2.9-11.1 Gy, median 5.9 Gy). Total tumour dose (30-76.8 Gy), age, sex distribution, and baseline chemosensory function were not significantly different between groups. Testing was performed for odour identification, odour discrimination, and olfactory thresholds. RESULTS: Odour discrimination, but not odour identification or odour threshold, was significantly decreased 2-6 weeks after begin of therapy in the OLF group. In addition, a significant effect of the radiation dose was observed for odour discrimination. More than 6 months after therapy, OLF group patients had significantly lower odour identification scores compared to the non-OLF group. CONCLUSION: As indicated through the non-significant change of olfactory thresholds, the olfactory epithelium is relatively resistant against effects of radiation. It is hypothesized that RT has additional effects on the olfactory bulb/orbitofrontal cortex responsible for the observed changes of suprathreshold olfactory function.

Adolescent↗
PubMed1996

Immunohistochemical localization of metallothionein in the olfactory pathway of dogs.

Dogs raised in the open air were used in this study. Metallothionein (MT) immunoreactivity was observed in the nucleus and/or cytoplasm of sustentacular cells of the olfactory epithelium in the nasal mucosa, whereas there was few MT-positive cells in the respiratory epithelium. MT immunoreactivity was also observed in astrocytes in all layers of the the olfactory bulb cortex; glial cells surrounding the glomeruli in the olfactory bulb showed prominent immunoreactivity for MT. Adult dogs exhibited stronger immunoreactivity for MT than young. Northern blot analysis demonstrated substantial levels of MT mRNA in the olfactory mucosa and olfactory bulb. Physiological roles of MT localized in the olfactory pathway of dogs were discussed.

Age Factors↗
PubMed1998

Detailed mapping of serotonin 5-HT1B and 5-HT1D receptor messenger RNA and ligand binding sites in guinea-pig brain and trigeminal ganglion: clues for function.

The similar pharmacology of the 5-HT1B and 5-HT1D receptors, and the lack of selective compounds sufficiently distinguishing between the two receptor subtypes, have hampered functional studies on these receptors. In order to provide clues for differential functional roles of the two subtypes, we performed a parallel localization study throughout the guinea-pig brain and the trigeminal ganglia by means of quantitative in situ hybridization histochemistry (using [35S]-labelled riboprobes probes for receptor messenger RNA) and receptor autoradiography (using a new radioligand [3H]alniditan). The anatomical patterns of 5-HT1B and 5-HT1D receptor messenger RNA were quite different. While 5-HT1B receptor messenger RNA was abundant throughout the brain (with highest levels in the striatum, nucleus accumbens, olfactory tubercle, cortex, hypothalamus, hippocampal formation, amygdala, thalamus, dorsal raphe and cerebellum), 5-HT1D receptor messenger RNA exhibited a more restricted pattern; it was found mainly in the olfactory tubercle, entorhinal cortex, dorsal raphe, cerebellum, mesencephalic trigeminal nucleus and in the trigeminal ganglion. The density of 5-HT(1B/1D) binding sites (combined) obtained with [3H]alniditan autoradiography was high in the substantia nigra, superior colliculus and globus pallidus, whereas lower levels were detected in the caudate-putamen, hypothalamus, hippocampal formation, amygdala, thalamus and central gray. This distribution pattern was indistinguishable from specific 5-HT1B receptor labelling in the presence of ketanserin under conditions to occlude 5-HT1D receptor labelling; hence the latter were below detection level. Relationships between the regional distributions of the receptor messenger RNAs and binding sites and particular neuroanatomical pathways are discussed with respect to possible functional roles of the 5-HT1B and 5-HT1D receptors.

Animals↗
PubMed1991

Glutathione levels in olfactory and non-olfactory neural structures of rats.

Olfactory receptor neurons are a CNS entry point for a wide variety of airborne substances. Therefore, it is probable that detoxification mechanisms are present in these neurons to neutralize such agents. Glutathione (GSH) is an essential component of several detoxification schemes, and in this study we examined the distribution and levels of GSH in the olfactory epithelium, olfactory bulb, cortex, hippocampus and cerebellum in neonatal, weanling, adult and aged rats. We report that GSH is primarily localized to the olfactory receptor neurons and their oxons within the olfactory epithelium. It is also localized within the glomerular neuropil and granule cells of the olfactory bulb. Levels of GSH in the olfactory epithelium and hippocampus do not change as a function of age, although GSH levels decrease in several brain regions, including the olfactory bulb, cerebellum and cortex.

Aging↗
PubMed2006

Dissociable codes of odor quality and odorant structure in human piriform cortex.

The relationship between odorant structure and odor quality has been a focus of olfactory research for 100 years, although no systematic correlations are yet apparent. Animal studies suggest that topographical representations of odorant structure in olfactory bulb form the perceptual basis of odor quality. Whether central olfactory regions are similarly organized is unclear. Using an olfactory version of fMRI cross-adaptation, we measured neural responses in primary olfactory (piriform) cortex as subjects smelled pairs of odorants systematically differing in quality and molecular functional group (as one critical attribute of odorant structure). Our results indicate a double dissociation in piriform cortex, whereby posterior regions encode quality (but not structure) and anterior regions encode structure (but not quality). The presence of structure-based codes suggests fidelity of sensory information arising from olfactory bulb. In turn, quality-based codes are independent of any simple structural configuration, implying that synthetic mechanisms may underlie our experience of smell.

Adult↗
PubMed1998

Glutamate-like immunoreactivity in axon terminals from the olfactory bulb to the piriform cortex.

A highly specific anti-glutamate monoclonal antibody, mAb2D7, was used together with light and electron microscopy to elucidate the role played by the amino acid glutamate in the projection from the olfactory bulb to the piriform cortex in the rat. By light microscopy, glutamate-like immunoreactivity was observed in neuronal cell bodies and in the neuropil of the piriform cortex. Double labelling experiments which involved injections of wheat germ agglutinin-horse--radish peroxidase into the olfactory bulb and a post-embedding immunogold method for electron microscopy revealed anterogradely labelled terminals making asymmetric synaptic contacts on dendrites in the piriform cortex which contained high levels of glutamate as assessed by quantification. These results further support a role for glutamate as a neurotransmitter in the efferent pathway of the rat olfactory bulb.

Animals↗