Nucleus raphe dorsalis in Alzheimer's disease: Neurofibrillary tangles and loss of large neurons

Yamamoto, Toru; Hirano, Atsushi

doi:10.1002/ana.410170608

Cited by 326 publications

(103 citation statements)

References 19 publications

(4 reference statements)

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“…A severe neuronal degeneration was observed in the basal nucleus of Meynert, locus coeruleus, the median raphe nucleus, medial amygdaloid nucleus, pedunculopontine tegmental nucleus, and substantia nigra, thereby confirming a number of earlier studies (Herzog and Kemper, 1980;Arendt et al, 1983;Mann et al, 1983;Shortridge et al, 1985;Yamamoto and Hirano, 1985;German et al, 1987;Jellinger, 1988;Woolf et al, 1989;Esiri et al, 1990;Goto et al, 1990;Aletrino et al, 1992;Förstl et al, 1992;Halliday et al, 1992;Scott et al, 1992). The overall extent of degeneration and the gradual variation of cell loss between different areas are also in agreement with previous reports (Zweig et al, 1988;ChanPalay et al, 1992;Arendt et al, 1995c).…”

Section: Apoe Gene Dose and Degeneration Of Subcortical Neuronssupporting

confidence: 87%

Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele

Arendt¹,

Schindler²,

Brückner³

et al. 1997

J. Neurosci.

302

172

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A relationship between the apolipoprotein E (apoE) genotype and the risk to develop Alzheimer's disease has been established recently. Apolipoprotein synthesis is implicated in developmental processes and in neuronal repair of the adult nervous system.In the present study, we investigated the influence of the apolipoprotein polymorphism on the severity of neuronal degeneration and the extent of plastic dendritic remodeling in Alzheimer's disease. Changes in length and arborization of dendrites of Golgi-impregnated neurons in the basal nucleus of Meynert, locus coeruleus, raphe magnus nucleus, medial amygdaloid nucleus, pedunculopontine tegmental nucleus, and substantia nigra were analyzed after three-dimensional reconstruction. Patients with either one or two apoE ⑀4 alleles not only showed a more severe degeneration in all areas investigated than in patients lacking the apoE 4 allele but also revealed significantly less plastic dendritic changes. ApoE ⑀4 allele copy number, furthermore, had a significant effect on the pattern of dendritic arborization. Moreover, the relationship between the intensity of dendritic growth and both the extent of neuronal degeneration and the stage of the disease seen in patients lacking the apoE ⑀4 allele was very weak in the presence of one ⑀4 allele and completely lost in patients homozygous for the ⑀4 allele.The results provide direct evidence that neuronal reorganization is affected severely in patients with Alzheimer's disease carrying the apoE ⑀4 allele. This impairment of neuronal repair might lead to a more rapid functional decompensation, thereby contributing to an earlier onset and more rapid progression of the disease.

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Section: Apoe Gene Dose and Degeneration Of Subcortical Neuronssupporting

confidence: 87%

Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele

Arendt¹,

Schindler²,

Brückner³

et al. 1997

J. Neurosci.

302

172

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“…The feasibility of this approach was first demonstrated in animal studies where selective lesioning of pyramidal neurons in the rat hippocampus (e.g., with kainic acid or ibotenic acid) resulted in parallel reductions in 5-HT 1A receptors providing a specific target for monitoring loss of these cells (5 (4). In surprisingly good agreement, dorsal raphe nucleus neuron loss of the same level (41% loss) has been reported in behaviorally characterized AD (19), while even greater loss occurs at late stages of AD that is paralleled by dense deposits of NFTs (20). Although the difference in [F-18]MPPF BP in other areas of the brain was not significantly different between AD and control groups (Table 1), we may not exclude that it would become obvious in a larger sample of ADs than used in this study or with more advanced disease.…”

Section: Discussionsupporting

confidence: 52%

Serotonin 1A receptors in the living brain of Alzheimer's disease patients

Kepe

Barrio

Huang

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

211

152

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[F-18]MPPF ͉ brain 5-HT1A receptors ͉ neuronal loss ͉ positron emission tomography E xtensive brain cell loss in vulnerable cortical neuronal populations is one of the most striking hallmarks of Alzheimer's disease (AD). Neuronal loss appears to be correlated with the presence of abundant intraneuronal neurofibrillary tangles (NFTs) and is also an excellent parameter to correlate with the degree of dementia (1). Among the vulnerable neurons affected in the earliest stages of the disease are large pyramidal neurons in the CA1 and subicular regions of hippocampus, a part of the medial temporal lobe (MTL) system supporting declarative memory (2). The pattern of neuronal loss in AD is distinctively different from the cell loss observed in normal aging and is highest in entorhinal cortex and hippocampus CA1 region (1, 3). Although these large pyramidal neurons are glutamatergic in nature, they receive inhibitory serotonergic input from the dorsal raphe nucleus via the serotonin 1A (5-HT 1A ) receptors located on their axonal hillock (4). The correlation between the loss of glutamatergic pyramidal neurons in CA1 field of hippocampus and the decrease in 5-HT 1A receptor densities in the same areas was demonstrated earlier by using in vitro 4- [F-18] and can be partially attributed to the neuronal loss in epileptic foci (6). Availability of methods for 5-HT 1A receptor density quantification with PET therefore offers an excellent opportunity for in vivo assessment of neuronal damage in 5-HT 1A receptor-rich areas in AD, particularly in hippocampus. In this work, changes in 5-HT 1A receptor densities in the living brain of AD patients (ADs) and mild cognitive impairment patients (MCIs) were also correlated with global and regional measures of glucose metabolic activity, with the extent and spatial distribution of the NFT͞␤-amyloid senile plaque deposition and with behavioral measures [e.g., Mini Mental State Exam (MMSE) and Buschke scores]. In vitro autoradiography in ADs and normal subject brain specimens was used in support of the observations in living subjects.

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“…Not only the breakdown of cholinergic neurotransmission (Whitehouse et al, 1981) but also the concurrent reduction of 5-HT function has been associated with the pathogenesis of AD (Curcio and Kemper, 1984;Yamamoto and Hirano, 1985). A number of behavioral and pharmacological studies point to a functional interaction between these two neurotransmitter systems in learning (Nilsson et al, 1988;Normile et al, 1990;Riekkinen et al, 1990;Cassel and Jeltsch, 1995).…”

Section: Introductionmentioning

confidence: 99%

Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and cholinergic basal forebrain nuclei during aging

Nyakas

Oosterink

Keijser

et al. 1997

Journal of Chemical Neuroanatomy

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Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and cholinergic basal forebrain nuclei during aging Nyakas, C; Oosterink, BJ; Felszeghy, K; deJong, GI; Korf, J; Luiten, PGM; Keijser, Jan N. Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Nyakas, C., Oosterink, BJ., Felszeghy, K., deJong, GI., Korf, J., Luiten, PGM., & Keijser, J. N. (1997). Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and cholinergic basal forebrain nuclei during aging. Journal of Chemical Neuroanatomy, 13(1), 53-61. https://doi.org/10.1016/S0891-0618(97)00025-2 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractThe effect of aging on 5-HT 1A receptor binding in several forebrain areas associated with the basal forebrain cholinergic system was investigated in rats of 3-, 24-and 30-months-old by receptor autoradiography and biochemical binding assay using [ 3 H]8-OH-DPAT as a ligand. Autoradiographic measurements demonstrated a marked region-specific decline of ligand binding in: (i) regions of the basal forebrain cholinergic cell groups, i.e. the medial septum, diagonal band nuclei and magnocellular nucleus basalis, (ii) the frontal and parietal neocortex and (iii) the dentate gyrus of the hippocampus. No change or only a slight decrease of the 5-HT 1A receptor density was found in other areas investigated: the CA1 and CA3 sectors of hippocampus, the cingular and perirhinal cerebral cortex and the lateral septum. The autoradiographic findings were substantiated by the biochemical binding assay, which revealed a comparable loss of 5-HT 1A receptor in the hippocampus and neocortex at the age of 30 months. The results clearly show that with increasing age the decrement of 5-HT 1A receptor binding in the rat forebrain is remarkably region-selective and particularly affects the cholinergic cell groups that innervate cortex and hippocampus. This phenomenon appears to be especially significant in relation to the neuronal substrates underlying the age-related alterations of mood and cognition. © 1997 Elsevier Science B.V.

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Nucleus raphe dorsalis in Alzheimer's disease: Neurofibrillary tangles and loss of large neurons

Cited by 326 publications

References 19 publications

Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele

Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele

Serotonin 1A receptors in the living brain of Alzheimer's disease patients

Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and cholinergic basal forebrain nuclei during aging

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