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At least 217 records · Page 12Linked to original sources
PubMed1989

Abnormalities in the NC1 domain of collagen type IV in GBM in canine hereditary nephritis.

Samoyed hereditary glomerulopathy (SHG) in dogs serves as a model for human X-linked hereditary nephritis (HN). We previously showed that glomerular capillaries of affected males did not stain by immunofluorescence (IF) using serum from a patient with Goodpasture's syndrome. Our goal in the present study was to determine whether the NC1 domain of the collagen type IV molecule, which contains Goodpasture antigen (GPA), could be demonstrated in these dogs, and to assess its immunological reactivity. By SDS-PAGE, NC1 in collagenase digests of glomerular basement membranes (GBM) of unaffected and carrier female dogs in the family with SHG showed 24 kilodalton (kD), 26 kD and 28 kD monomer, and 46 kD and 47 kD dimer components, but the 24 kD monomer was diminished in the affected males. By IF, a rabbit antibody to NCl stained glomerular capillaries of unaffected, affected male, and carrier female dogs. In contrast, a human anti-GBM plasmapheresis fluid (PPF) stained glomerular capillaries of only the unaffected and carrier female dogs. By RIA, both antibodies reacted strongly with NCl in collagenase digests of GBM of the unaffected and carrier female dogs, but showed reduced reactivity with NCl of affected males. By Western blotting, both antibodies bound to dimers and 24 kD and 26 kD monomers of the NCl domain in collagenase digests of GBM of unaffected and carrier female dogs. However, in affected males, the rabbit anti-NCl antibody did not bind to the 24 kD monomer, while the human anti-GBM PPF showed weak binding to the 24 kD and 26 kD monomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Biochemical characterization of a lysosomal protease deficient in classical late infantile neuronal ceroid lipofuscinosis (LINCL) and development of an enzyme-based assay for diagnosis and exclusion of LINCL in human specimens and animal models.

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL), a progressive and fatal neurodegenerative disease of childhood, results from mutations in a gene (CLN2) that encodes a protein with significant sequence similarity to prokaryotic pepstatin-insensitive acid proteases. We have developed a sensitive protease activity assay that allows biochemical characterization of the CLN2 gene product in various human biological samples, including solid tissues (brain and chorionic villi), blood (buffy coat leukocytes, platelets, granulocytes, and mononuclear cells), and cultured cells (lymphoblasts, fibroblasts, and amniocytes). The enzyme has a pH optimum of 3.5 and is rapidly inactivated at neutral pH. A survey of fibroblasts and lymphoblasts demonstrated that lack of activity was associated with LINCL arising from mutations in the CLN2 gene but not other neuronal ceroid lipofuscinoses (NCLs), including the CLN6 variant LINCL, classical infantile NCL, classical juvenile NCL, and adult NCL (Kufs' disease). A study conducted using blood samples collected from classical LINCL families whose affliction was confirmed by genetic analysis indicates that the assay can distinguish homozygotes, heterozygotes, and normal controls and thus is useful for diagnosis and carrier testing. Analysis of archival specimens indicates that several specimens previously classified as LINCL have enzyme activity and thus disease is unlikely to arise from mutations in CLN2. Conversely, a specimen previously classified as juvenile NCL lacks pepinase activity and is associated with mutations in CLN2. In addition, several animals with NCL-like neurodegenerative symptoms [mutant strains of mice (nclf and mnd), English setter, border collie, and Tibetan terrier dogs, sheep, and cattle] were found to contain enzyme activity and are thus unlikely to represent models for classical LINCL. Subcellular fractionation experiments indicate that the CLN2 protein is located in lysosomes, which is consistent with its acidic pH optimum for activity and the presence of mannose 6-phosphate. Taken together, these findings indicate that LINCL represents a lysosomal storage disorder that is characterized by the absence of a specific protease activity.

Age of Onset↗
PubMed2001

Cardiac pathology in neuronal ceroid lipofuscinoses--a clinicopathologic correlation in three patients.

We report the clinical details and the pathology of the heart at autopsy of three neuronal ceroid lipofuscinosis (NCL) patients. Two patients were diagnosed as classical juvenile NCL and one as a variant juvenile NCL (JNCL) with granular osmiophilic deposits (GRODs). Cardiac findings during life were retrospectively evaluated and included left ventricular hypertrophy with repolarization disturbances (ECG findings) in two patients with classical JNCL and severe bradycardia with periods of sinus arrest in one of them, severe supraventricular tachycardias during anaesthesia in the variant JNCL-patient. At autopsy myocardial and valvular storage of lipopigments, diagnostic for NCL, was observed histologically and confirmed ultrastructurally in all three cases. In two patients with JNCL the storage was associated with hypertrophy and dilation of both ventricles, degenerative myocardial changes, interstitial fibrosis and fatty replacement. Abundant accumulation and degeneration were seen in all components of the conduction system in three patients, which outreached at several places by far the storage of the adjacent myocardium. Our observations indicate a prominent involvement of the heart in NCL, with preference of storage for the conduction system of the heart.

Adult↗
PubMed2006

[The role of the ophthalmologist in the management of juvenile neuronal ceroid lipofuscinosis].

BACKGROUND: Neuronal ceroid lipofuscinoses (NCL) are storage diseases leading to severe somatic and mental deterioration with blindness and death. To date, there are no therapeutic options. Juvenile NCL (JNCL), also known as Batten's disease, is one of the most prevalent forms of NCL. MATERIALS AND METHODS: A 6-year-old boy with the primary diagnosis of retinitis pigmentosa was examined. The parents reported a rapid deterioration of vision during the past months. In view of this history, additional, non-ophthalmological diagnostic procedures have been performed (peripheral blood smear, molecular genetics). RESULTS: The eye examination showed a considerable reduction of visual acuity, a concentric visual field constriction, an extinguished electroretinogram and a bull's eye maculopathy. The peripheral blood smear revealed vacuolated lymphocytes. Molecular genetic investigation confirmed the diagnosis of juvenile NCL by detecting a homozygous (1-kb deletion of the CLN3-gene). CONCLUSIONS: The ophthalmologist plays a key role for an early diagnosis of juvenile NCL. An early diagnosis is important for the affected families because only then they can handle this stroke of fate.

Child↗
PubMed1996

Localized proton magnetic resonance spectroscopy of cerebral metabolic disturbances in children with neuronal ceroid lipofuscinosis.

Cerebral metabolic abnormalities in five children with infantile (1), late infantile (1), and juvenile (3) neuronal ceroid lipofuscinosis (NCL) were noninvasively assessed by localized proton magnetic resonance spectroscopy (MRS). Infantile NCL was characterized by a complete loss of N-acetylaspartate (NAA, neuronal marker), a marked reduction of creatines (Cr) and choline-containing compounds (Cho), and an elevation of myo-inositol (Ins, glial marker) and lactate (Lac) in both gray and white matter. Reduced NAA and elevated Lac were also detected in gray and white matter of late infantile NCL, but in this case not only Ins but also Cr and Cho were increased in white matter. In contrast to the infantile forms, juvenile NCL exhibited normal metabolic profiles. In one patient disease progression was indicated by reduced NAA and Cr in gray matter in a follow-up study after four years. The present findings in NCL are consistent with irreversible and generalized neuroaxonal loss as well as alterations of white matter glia similar to those found in leukodystrophies. The severity of metabolic disturbances correlates with clinical symptoms and decreasing age of onset.

Aspartic Acid↗
PubMed2001

A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and inhibits promoter activity.

Many sequences in eukaryotic genomes have the potential to adopt a left-handed Z-DNA conformation. We used a previously described assay based on the binding of a mAb to Z-DNA to inquire whether Z-DNA is formed in the rat nucleolin (Ncl) gene in metabolically active, permeabilized nuclei. Using real-time PCR to measure Z-DNA formation, the potential Z-DNA sequence element Z1 [(CA)(10)(CG)(8)] in the promoter region was found to be enriched 571- to 4,040-fold in different cell lines, whereas Z2 [AC(GC)(5)CCGT(CG)(2)] in the first intron was enriched 12- to 34-fold. Ncl promoter activity was 1.5- to 16-fold stronger than that of the simian virus 40 promoter and enhancer. This activity was further increased 36-54% when Z1 was deleted. The inhibitory effect of Z1 on Ncl promoter activity was independent of location and orientation. The Ncl Z1 element is identical to the genetic marker D9Arb5. Five allelic variants of Z1 were identified by sequence analysis of genomic DNA from various rats. The two most common alleles differed significantly (up to 27%) in their capacity to inhibit Ncl promoter activity. This finding suggests that differences in Z-DNA formation by polymorphic dinucleotide repeats may be one of the factors contributing to genetic variation.

Alleles↗
PubMedDate not supplied

Neuronal ceroid lipofuscinosis: an ultrastructural, genetic, and clinical study report.

The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited neurodegenerative conditions associated with storage of lipopigments in brain tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural level it is possible to distinguish 5 different patterns of osmiophilic lipopigments: usual lipofuscin, fingerprint deposits, granular profiles, curvilinear bodies, and microtubular aggregates. The concept that each ultrastructural pattern was the counterpart of a specific clinical type has been proved not to be true. Advances in molecular genetic techniques have allowed the identification of defective genes and their protein products in several NCL clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not only in neuronal cells, but also in several other sites, such as trophoblastic cells, thus permitting prenatal diagnosis. In spite of recent advances in immunohistochemical identification of biochemical markers, the ultrastructural identification of lipofuscinic pigments remains the gold standard to identify NCL, together with clinical aspects and respective gene defects. This study describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3 juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In these patients, genetic analysis was also performed.

Ceroid↗
PubMed2000

Molecular diagnosis of and carrier screening for the neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are a large group of autosomal recessive lysosomal storage disorders with both enzymatic deficiency and structural protein dysfunction. Three typical forms, the infantile (INCL), late-infantile (LINCL), and juvenile (JNCL), are among the most common childhood-onset neurodegenerative disorders. They result from mutations on genes CLN1, CLN2, and CLN3, respectively. We determined that the mutations 223A --> G and 451C --> T in CLN1, T523-1G --> C, and 636 C --> T in CLN2, and deletion of a 1.02-kb genomic fragment in CLN3 are the five common mutations for NCL. To offer clinical genetic testing for the NCLs, we have developed simple and quick PCR-based molecular tests for detecting INCL-, LINCL-, and JNCL-affected individuals from 180 NCL families (27 INCL, 76 LINCL, and 77 JNCL). The sensitivity of testing to detect NCL patients among clinically suspected individuals was determined to be 78% (21/27) for INCL, 66% (54/76) for LINCL, and 75% (58/77) for JNCL. When molecular screening for carriers was conducted among the normal siblings or parents of the probands, we identified two carriers out of three individuals tested for INCL, 20/56 (35.7%) carriers for LINCL, and 48/106 (45.3%) carriers for JNCL families. In addition, 5% (9/180) of NCL patients revealed genetic heterogeneity and were reclassified. Seven patients previously diagnosed as having JNCL were now found to carry mutations of CLN2 (5/7) or CLN1 (2/7) and 2 with late-infantile onsets were identified as carrying mutations of CLN1. Our data demonstrate the importance of DNA testing to detect accurately both affected individuals and carriers in NCL families.

Adolescent↗
PubMed2005

Drug discovery in the kinase inhibitory field using the Nested Chemical Library technology.

Kinase inhibitors are at the forefront of modern drug research, where mostly three technologies are used for hit-and-lead finding: high throughput screening of random libraries, three-dimensional structure-based drug design based on X-ray data, and focused libraries around limited number of new cores. Our novel Nested Chemical Library (NCL) (Vichem Chemie Research Ltd., Budapest, Hungary) technology is based on a knowledge base approach, where focused libraries around selected cores are used to generate pharmacophore models. NCL was designed on the platform of a diverse kinase inhibitory library organized around 97 core structures. We have established a unique, proprietary kinase inhibitory chemistry around these core structures with small focused sublibraries around each core. All the compounds in our NCL library are stored in a big unified Structured Query Language database along with their measured and calculated physicochemical and ADME/toxicity (ADMET) properties, together with thousands of molecular descriptors calculated for each compound. Biochemical kinase inhibitory assays on selected, cloned kinase enzymes for a few hundred NCL compound sets can provide sufficient biological data for rational computerized design of new analogues, based on our pharmacophore model-generating 3DNET4W QSPAR (quantitative structure-property/activity relationships) approach. Using this pharmacophore modeling approach and the ADMET filters, we can preselect synthesizable compounds for hit-and-lead optimization. Starting from this point and integrating the information from QSPAR, high-quality leads can be generated within a small number of optimization cycles. Applying NCL technology we have developed lead compounds for several validated kinase targets.

Algorithms↗
PubMed2002

Neuronal ceroid lipofuscinosis in Merino sheep.

OBJECTIVE: To characterise neuronal ceroid lipofuscinosis (NCL) in Merino sheep. DESIGN: A prospective clinical, pathological, biochemical and genetic study. PROCEDURE: NCL cases were studied from a medium-wool Merino flock, the stud of origin of its replacement rams, and an experimental flock established at the University of Sydney. RESULTS: Behavioural changes and visual impairment were first detected at 7 to 12 months of age and progressed, with associated motor disturbances and at later stages seizures, to premature death by 27 months of age. At necropsy there was severe cerebrocortical atrophy associated with neuronal loss, astrocytosis and the presence in neurons of eosinophilic intracytoplasmic storage bodies with the characteristics of a lipopigment. In the retina there was progressive loss of photoreceptor cells. Storage bodies isolated from fresh brain, liver and pancreas formed electron-dense aggregates and coarse multilamellar and fine fingerprint profiles ultrastructurally, and consisted mainly of the hydrophobic protein, subunit c of mitochondrial ATP synthase. A homozygosity mapping approach localised the gene causing the disease in Merino sheep to the chromosomal region (OAR7q13-15) associated with NCL in South Hampshire sheep. CONCLUSION: NCL in Merino sheep is a subunit c-storing disease, clinically and pathologically similar to NCL in South Hampshire sheep. We propose that the disease in both breeds represents mutation at the same gene locus in chromosomal region OAR7q13-15.

Animals↗
PubMed2002

Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics.

The mnd mouse, a model of neuronal ceroid lipofusinosis (NCL), has a profound vitamin E deficiency in sera and brain, associated with cerebral deterioration characteristic of NCL. In this study, the vitamin E deficiency is corrected using dietary supplementation. However, the histopathological features associated with NCL remained. With use of a bioinformatics approach based on high-resolution solid and solution state 1H-NMR spectroscopy and principal component analysis (PCA), the deficits associated with NCL are defined in terms of a metabolic phenotype. Although vitamin E supplementation reversed some of the metabolic abnormalities, in particular the concentration of phenylalanine in extracts of cerebral tissue, PCA demonstrated that metabolic deficits associated with NCL were greater than any effects produced from vitamin E supplementation. These deficits included increased glutamate and N-acetyl-L-aspartate and decreased creatine and glutamine concentrations in aqueous extracts of the cortex, as well as profound accumulation of lipid in intact cerebral tissue. This is discussed in terms of faulty production of mitochondrial-associated membranes, thought to be central to the deficits in mnd mice.

Animals↗
PubMed2005

[Pitfalls in the clinical and electroencephalographic diagnosis of ceroid lipofuscinosis].

Neuronal ceroid lipofuscinosis (NCL) were traditionally classified according to age of onset and clinical features in four main groups. Recently, a combination of clinical, ultra structural and genetics data led to the recognition of eight forms of NCL, providing a more precise framework to classify atypical cases. By the other hand, it was shown that mutations in the same gene could be responsible for a large variety of clinical phenotypes. The objective of this study is to describe two brothers with clinical and electroencephalographic abnormalities characteristic of juvenile NCL, but with ultra structural abnormalities suggestive of late infantile NCL. Electroencephalogram is useful for clinical diagnosis of NCL but it is not helpful in its classification.

Adolescent↗
PubMed1999

Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment.

The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative disorders with onset from infancy to adulthood that are manifested by blindness, seizures, and dementia. In NCL, lysosomes accumulate autofluorescent proteolipid in the brain and other tissues. The mnd/mnd mutant mouse was first characterized as exhibiting adult-onset upper and lower motor neuron degeneration, but closer examination revealed early, widespread pathology similar to that seen in NCL. We used the autofluorescent properties of accumulated storage material to map which CNS neuronal populations in the mnd/mnd mouse show NCL-like pathological changes. Pronounced, early accumulation of autofluorescent lipopigment was found in subpopulations of GABAergic neurons, including interneurons in the cortex and hippocampus. Staining for phenotypic markers normally present in these neurons revealed progressive loss of staining in the cortex and hippocampus of mnd/mnd mice, with pronounced hypertrophy of remaining detectable interneurons. In contrast, even in aged mutant mice, many hippocampal interneurons retained staining for glutamic acid decarboxylase. Treatment with insulin-like growth factor-1 partially restored interneuronal number and reduced hypertrophy in some subregions. These results provide the first evidence for the involvement of interneurons in a mouse model of NCL. Moreover, our findings suggest that at least some populations of these neurons persist in a growth factor-responsive state.

Aging↗
PubMed2003

Dissociation of extinction and behavioral disinhibition: the role of NMDA receptors in the pigeon associative forebrain during extinction.

Extinction is a unique learning process that requires the alteration of stimulus-response associations such that the organism ceases to respond to a previously rewarded stimulus. Extinction is mostly studied with fear conditioning and is impaired by lesions of the prefrontal cortex as well as by blockade of NMDA receptors in the amygdala. Because previous tasks could not clearly disambiguate extinction from behavioral disinhibition, the underlying process was difficult to define. In this study, we examined the possible role of NMDA receptors and the pigeon "prefrontal cortex," the neostriatum caudolaterale (NCL), for extinction of appetitive instrumental conditioning. We used a new design that discerns extinction from behavioral disinhibition. Our results demonstrate that NCL lesions cause deficits neither in extinction learning nor in extinction recall. However, blockade of NMDA receptors in the pigeon NCL by DL-AP-5 drastically impairs extinction learning without producing behavioral disinhibition or deficits in extinction recall. We suggest that NMDA receptors in the NCL contribute to the establishment of a learning process that selectively signals the change in value of the instrumental stimulus. Although NCL plays a key role for extinction learning, other structures can subsume similar functions after postlesional regeneration.

Animals↗
PubMed2006

[Neuronal ceroid lipofuscinoses].

BACKGROUND: Neuronal ceroid lipofuscinoses (NCL) is a group of degenerative neurological diseases. The diseases are autosomally recessively inherited and are characterized by the accumulation of fluorescent ceroid and lipofuscin in neuronal cells in the brain and in extraneuronal cells. The aim of this review was to assess and to summarize research related to diagnostics and treatment of NCL. MATERIAL AND METHODS: The article is built on own experience and systematic searches on PubMed, Medline, PsychInfo and the Internet. RESULTS AND INTERPRETATION: Three main types of NCL with childhood onset are recognised; an infantile, a late infantile, and a juvenile type. One NCL type starts in adulthood. In Norway the juvenile type is diagnosed most frequently. The diseases are rare. The incidence rates in different countries range from 0.5 to 8.0 per 100,000 live births. The main features include impaired vision, failure of psychomotor development, seizures and premature death. Prior to availability of genetic testing, the clinical status, ophthalmologic examination, examination of blood cells for deposited material (vacuolised lymphocytes) and neurophysiological examinations were the most important methods of confirming the diagnosis. Recent genetic findings have established that defects in at least six different genes underlie the various forms of NCL. There is no curative treatment. Scientists are trying to develop treatment using enzyme replacement, gene therapy, stem cell transplantation and pharmacotherapy. Symptomatic and palliative treatment is therefore essential.

Adult↗
PubMed1988

Double-labelled nigral compacta and reticulata cells from injections in the reticular formation and in the striatum. An experimental study using retrograde double labelling with HRP and iron-dextran in the rat.

14 rats were studied for the nigro-reticular projection. All animals had a relatively large quantity of dextran-fer injected in the middle of the striatum (to label the nigro-striatic cells and to facilitate distinction between the compacta and reticulata zones). 5 days later, HRP was injected in the reticular formation of the ponto-mesencephalic junction (in the ncl. pedunculo-pontinus, pontis oralis et caudalis, and in the caudal parts of the ncl. cuneiformis). Retrogradely labelled nigro-striatic, nigro-reticular and double-labelled nigrostriato-reticular cells were found. In the zona compacta substantiae nigrae, about 1/3 of the total number of labelled cells were identified as nigro-striatic, 1/3 as nigro-reticular, and 1/3 as collateralizing to the striatum and the reticular formation. In the zona reticulata substantiae nigrae, 2/3 of the total number of labelled cells constituted the nigro-reticular and 1/6 the nigro-striatic projections, while 1/6 collateralized to the striatum and the reticular formation. Retrograde HRP transport in the non-collateralized nigro-reticular and in the collateralized nigrostriato-reticular projections originated mainly from the ncl. pedunculo-pontinus and ncl. pontis oralis. Retrograde transport from the ncl. pontis caudalis was much less prominent. The numerous connections projecting from the zona compacta to the reticular formation point to the essentially dopaminergic nature of this projection. Collaterals of the nigro-striatic projection directed towards the reticular formation have not yet been described in the literature available to the author.

Animals↗
PubMed1986

Depressed neutrophil chemotactic stimuli in supernatants of ionophore-treated polymorphonuclear leukocytes from selenium-deficient goats.

The effect of dietary selenium (Se) deficiency on the generation of neutrophil chemotactic factors from goat polymorphonuclear leukocytes (PMN) was studied. Polymorphonuclear leukocytes were isolated from 2 groups of crossbred goats. One group (n = 3) was fed a diet deficient in Se; the other (n = 3) was fed a diet adequate in Se. The PMN from each goat were stimulated with calcium ionophore A23187 and supernatants were collected. Each supernatant was immediately assayed for its ability to elicit neutrophil chemotaxis (NCT) and neutrophil chemokinesis by the Boyden chamber technique and neutrophil chemiluminescence (NCL) by the luminol-dependent chemiluminescence assay. Measurements from each group were compared, using the Student's t test. There was no significant difference (P greater than 0.01) in neutrophil chemokinesis elicited by supernatants derived from stimulated PMN from the 2 groups. However, supernatants derived from PMN of goats fed the Se-deficient diet had a significantly decreased capacity (P less than 0.01) to stimulate NCT and NCL. In vitro incubation of PMN with Se before ionophore treatment produced supernatants with increased NCL stimulation (P less than 0.05), but none with increased NCT stimulation (P greater than 0.05). However, both activities were restored after goats fed the Se-deficient diet (P less than 0.01) were given Se subcutaneously. Seemingly, dietary Se deficiency is associated with depressed PMN generation of factors that stimulate NCT and NCL. In contrast to NCL factors, synthesis of factors stimulating NCT probably was not associated directly with PMN glutathione peroxidase concentration.

Animals↗
PubMed1985

Gudden's tegmental nuclei and their connections to the hypothalamus and the reticular formation. I. An experimental study using retrograde labelling with HRP or iron-dextran in the rat.

31 rats were studied for the retrograde transport of HRP or dextran-fer from the corpus mamillare, anterior hypothalamus or reticular formation to the cells of the ventral (VG) and dorsal (DG) Gudden's tegmental nuclei. Judging by the position of the projection cells the VG was found divisible into the peripheral and central parts, a finding out of line with the conventional cytoarchitectonic division. The two parts differ in part of their projections. While both project jointly to the medial mamillary body, the peripheral part has a separate projection to the whole lateral hypothalamus whereas the central part projects also to the RF (ncl. pedunculopontinus and ncl. pontis oralis). The group of cells localized close to the cranial field of the VG, cytoarchitectonically referred to as the pars compacta ncl. centralis superioris, has the same projections as the external parts of the VG and can, therefore, be seen as a component of the VG peripheral part like the cells over the caudal field of the VG (pars intrafascucularis localized already among FLM fibres). The central part is made up of cells localized in the middle portions of the bulk of the VG cells. The dorsal Gudden's tegmental nucleus projects its ventral part to the lateral mamillary body, to the medial and lateral hypothalamus and to the RF (ncl. pontis oralis). The dorsal part of the DG projects solely to the RF (ncl. pontis oralis).

Animals↗