Ultrastructure of aberrant serotonin‐immunoreactive fibers in the caudate putamen complex of the aged rat

Luijtelaar, M. G. P. A. van; Wouterlood, Floris G.; Tonnaer, J. A. D. M.; Steinbusch, Harry W.M.

doi:10.1002/syn.890080303

Cited by 11 publications

(2 citation statements)

References 16 publications

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“…These features become gradually more pronounced with age. Using electron microscopy, Van Luijtelaar et al (1992b) demonstrated the presence of distorted mitochondria and vacuolated membranes in the serotoninergic fibers of the normal aged rat. They considered these changes to reflect degeneration.…”

Section: Discussionmentioning

confidence: 99%

Age‐related degeneration of the serotoninergic fibers in the zitter rat brain

Ueda

Aikawa

Ishizuya‐Oka

et al. 1998

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The serotonin neuron system was studied using immunohistochemical and neurochemical techniques in zitter mutant rats aged 1-14 months, which are characterized by abnormal metabolism of superoxides. The morphology of the serotoninergic neuron system and the serotonin level in the zitter rat were compared to those of age-matched Sprague-Dawley (SD) rats. Up to age 4 month, the density and distribution of serotoninergic fibers in the zitter rat brain were similar to those of control rats. However, several serotoninergic fibers with abnormal morphology, characterized by swollen varicosities, were observed in the cerebral cortex and caudate putamen of 6-month-old zitter rats. The density and distribution of these fibers in other regions of the brain were similar to those of control rats. The abnormal serotoninergic fibers increased in number and extended into other regions of the brain such as the thalamus, hippocampus, and vestibular nucleus. On the other hand, the density of normal serotoninergic fibers decreased throughout the brain of the 14-month-old zitter rat. Abnormal serotoninergic fibers have also been reported in the brain of normal older (24 months) SD rats. Neurochemical analysis revealed lower levels of serotonin, and 5-hydroxyindoleacetic acid, in all cortical areas (prefrontal, parietal, and occipital cortices), the caudate putamen, and the hippocampus of 12-month-old zitter rats. Levels differed significantly in the parietal cortex and hippocampus between the zitter and SD rats. Based on the morphological and neurochemical similarities, the present results suggest that age-related degeneration of serotoninergic fibers occurs in the zitter rat brain. Furthermore, degeneration of serotoninergic fibers appears to be induced by superoxide species. Thus, the zitter rat may provide a good model for studying the neurotoxic effects of superoxide species on the serotoninergic neuron system.

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Section: Discussionmentioning

confidence: 99%

Age‐related degeneration of the serotoninergic fibers in the zitter rat brain

Ueda

Aikawa

Ishizuya‐Oka

et al. 1998

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“…Although 5-HT axon terminals (varicosities) in normal adult rat neostriatum do not often make synaptic membrane specializations (Soghomonian et a!., 1989;Van Luijtelaar et a!., 1991), the frequency of junctional terminals found in the 5-HT-hyperinnervated neostriatum does not change ('-~10%),indicating a greater absolute number of synaptic 5-HT varicosities (Descarries et a!., 1992). The proportion of the various cellular constituents in the immediate microenvironment of these 5-HT terminals also remains unchanged, furthering the view that these varicosities are mostly distributed randomly in relation to eventual cellular targets.…”

Section: Neonatal 6-ohda and 5-ht Neuronsmentioning

confidence: 99%

Serotonin Neural Adaptations to Ontogenetic Loss of Dopamine Neurons in Rat Brain

Kostrzewa

Reader

Descarries

1998

Journal of Neurochemistry

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In rat, the neonatal destruction of nigrostriatal dopamine (DA) neurons by intracerebral administration of 6‐hydroxydopamine entails dramatic changes in serotonin (5‐hydroxytryptamine, 5‐HT) as well as DA function. Most striking is the 5‐HT hyperinnervation of the adult neostriatum, associated with increases in density of various 5‐HT receptor subtypes and enhanced neuronal responsiveness to the iontophoretic application of 5‐HT and its 5‐HT1B/2C and 5‐HT2A/2C receptor agonists, m‐chlorophenylpiperazine and iododimethoxyphenylaminopropane. The topographical distribution of these changes is consistent with up‐regulation and/or increased production and transport of 5‐HT1B and 5‐HT2A receptors by the neostriatal projection neurons, as confirmed for the 5‐HT2A receptor in a recent in situ hybridization study. It is interesting that this study has also shown that increases in both 5‐HT2A binding and mRNA level were abolished by chronic pretreatment with the DA agonists, apomorphine and SKF 38393, suggesting a regulatory influence of DA in the expression of this 5‐HT receptor. D1 receptor binding is known to be slightly reduced in the rostral neostriatum of these rats, a down‐regulation apparently imputable to a reduced rate of synthesis of the receptor. In contrast, D2 receptor binding is increased throughout the DA‐denervated and 5‐HT‐hyperinnervated neostriatum, perhaps due to some post‐transcriptional modifications. Stereotyped and motor behaviors induced by systemic treatment with D1 and D2 agonists are markedly enhanced in these rats (behavioral supersensitivity), although priming is commonly required to unmask a latent D1 supersensitivity. In the case of oral activity, however, overt behavioral supersensitivity is induced by D1 as well as D2 agonists. Moreover, there is overt supersensitivity of oral activity in response to the 5‐HT receptor agonist m‐chlorophenylpiperazine, which is presumably imputable to 5‐HT2C receptors and may be demonstrated even in the absence of supersensitivity to D1 receptor agonist. 5‐HT adaptations, therefore, seem to play a role not only in the abnormal spontaneous behavior, but also in the behavioral supersensitivity to 5‐HT as well as DA receptor agonists in these rats.

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The serotoninergic bulbospinal system and brainstern‐spinal cord content of serotonin‐, TRH‐, and substance P‐like immunoreactivity in the aged rat with special reference to the spinal cord motor nucleus

Johnson

Ulfhake

Dagerlind

et al. 1993

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The 5-hydroxytryptamine (5HT) containing bulbospinal pathway was studied with immunohistochemical (IF) and chemical techniques in 2-3 and 30 months old male Sprague-Dawley rats. The coexisting neuropeptides substance P (SP), thyrotropin-releasing hormone (TRH) and galanin were also analysed. Furthermore, the expression of mRNA encoding aromatic L-amino acid decarboxylase (AADC), prepro-TRH, and preprotachykinin (prepro-SP) was analysed with in situ hybridization (ISH) in the midline raphé nuclei inthe lower brainstem. The results showed a decreased number of axonal 5HT fibers with a normal morphology in the ventral horn of the aged rat lumbosacral spinal cord, and several 5HT immunoreactive (IR) fibers with an aberrant morphology, suggestive of axonal degeneration, were intermingled. This was evident in both the dorsal and ventral horn of the spinal cord. The 5HT-IR fibers with an aberrant morphology usually also contained TRH-and/or SP- and/or galanin-like immunoreactivity (LI) in the ventral horn. These signs of degeneration were clearly less evident in the thoracic and cervical spinal cord segments. Moreover, these changes varied between aged litter-mates. This was in agreement with behavioural signs of motor disturbances, present in about 40% of the aged rats and which in all cases were confined to the hindlimbs. Chemical analyses disclosed significantly lower levels of TRH-LI and, in particular, SP-LI in both the ventral and dorsal quandrants of the spinal cord in the aged rat compared to young adults. The differences were largest in the lumbar regions of the spinal cord. Corresponding analysis of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in the same tissue specimens revealed largely unaltered levels of 5HT and a slight increase in 5HIAA, indicating the possibility of an increased 5HT turnover in the aged rat spinal cord. Neurons in nucleus raphé obscurus and nucleus raphé pallidus were immunoreactive to 5HT, and after pretreatment with colchicine to TRH-, SP-, and galanin-LI as well. There was no obvious difference in number of labeled cells, or labeling intensity, between colchicine-treated young adult and aged rats, although, in the corresponding region of medulla oblongata, chemical analysis disclosed significantly lower levels of 5HT, TRH, and, in particular, SP in untreated aged rats. In contrast, in situ hybridization analysis revealed increased mRNA levels encoding prepro-TRH and prepro-SP in old rats, while mRNA content encoding AADC mRNA was similar in young adult and aged rats.(ABSTRACT TRUNCATED AT 400 WORDS)

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Ultrastructure of aberrant serotonin‐immunoreactive fibers in the caudate putamen complex of the aged rat

Cited by 11 publications

References 16 publications

Age‐related degeneration of the serotoninergic fibers in the zitter rat brain

Age‐related degeneration of the serotoninergic fibers in the zitter rat brain

Serotonin Neural Adaptations to Ontogenetic Loss of Dopamine Neurons in Rat Brain

The serotoninergic bulbospinal system and brainstern‐spinal cord content of serotonin‐, TRH‐, and substance P‐like immunoreactivity in the aged rat with special reference to the spinal cord motor nucleus

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