Expression of tyrosine hydroxylase and vasopressin in magnocellular neurons of salt-loaded aged rats.
ABSTRACT Tyrosine hydroxylase (TH) is expressed in catecholaminergic neurons. However, under certain conditions it is also ectopically expressed in magnocellular neurons of the hypothalamus. To test the hypothesis that this expression of TH is related to the cellular activation of these neurons and/or to the vasopressin (VP) expression, we studied the expression of both TH and VP in control and salt-loaded aged rats. Our results demonstrate that aged rats show a marked TH expression in VP cells which is further increased by osmotic stimulation in the absence of increase in VP synthesis in the supraoptic nucleus. The presence of TH-immunopositive dendritic swellings in the ventral part of this nucleus reveals the high state of plasticity of these neurons. Furthermore, the lack of several actors of catecholamine biosynthesis in these neurons suggests a different role for TH. This study further demonstrates an ectopic expression of TH in hypothalamic neurons of aged rats and a TH expression linked to the activation of VP neurons but unrelated to VP synthesis.
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ABSTRACT: Besides the dopaminergic (DA-ergic) neurons possessing the whole set of enzymes of DA synthesis from l-tyrosine and the DA membrane transporter (DAT), the neurons partly expressing the DA-ergic phenotype have been first discovered two decades ago. Most of the neurons express individual enzymes of DA synthesis, tyrosine hydroxylase (TH) or aromatic l-amino acid decarboxylase (AADC) and lack the DAT. A list of the neurons partly expressing the DA-ergic phenotype is not restricted to so-called monoenzymatic neurons, e.g. it includes some neurons co-expressing both enzymes of DA synthesis but lacking the DAT. In contrast to true DA-ergic neurons, monoenzymatic neurons and bienzymatic non-dopaminergic neurons lack the vesicular monoamine transporter 2 (VMAT2) that raises a question about the mechanisms of storing and release of their final synthetic products. Monoenzymatic neurons are widely distributed all through the brain in adulthood being in some brain regions even more numerous than DA-ergic neurons. Individual enzymes of DA synthesis are expressed in these neurons continuously or transiently in norm or under certain physiological conditions. Monoenzymatic neurons, particularly those expressing TH, appear to be even more numerous and more widely distributed in the brain during ontogenesis than in adulthood. Most populations of monoenzymatic TH neurons decrease in number or even disappear by puberty. Functional significance of monoenzymatic neurons remained uncertain for a long time after their discovery. Nevertheless, it has been shown that most monoenzymatic TH neurons and AADC neurons are capable to produce l-3,4-dihydroxyphenylalanine (L-DOPA) from l-tyrosine and DA from L-DOPA, respectively. L-DOPA produced in monoenzymatic TH neurons is assumed to play a role of a neurotransmitter or neuromodulator acting on target neurons via catecholamine receptors. Moreover, according to our hypothesis L-DOPA released from monoenzymatic TH neurons is captured by monoenzymatic AADC neurons for DA synthesis. Such cooperative synthesis of DA is considered as a compensatory reaction under a failure of DA-ergic neurons, e.g. in neurodegenerative diseases like hyperprolactinemia and Parkinson's disease.Thus, a substantial number of the brain neurons express partly the DA-ergic phenotype, mostly individual complementary enzymes of DA synthesis, serving to produce DA in cooperation that is supposed to be a compensatory reaction under the failure of DA-ergic neurons.Journal of chemical neuroanatomy 09/2009; 38(4):241-56. · 1.75 Impact Factor
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ABSTRACT: In addition to the monoaminergic (MA-ergic) neurons possessing the whole set of enzymes of monoamine (MA) synthesis from the precursor amino acid and the MA membrane transporter, the neurons partly expressing the MA-ergic phenotype have been first discovered almost twenty years ago. Most of the neurons expressing individual enzymes of MA synthesis lack the MA transporter. These so-called monoenzymatic neurons are widely distributed throughout the brain in adult mammals being even more numerous than MA-ergic neurons. Individual enzymes of MA synthesis are expressed continuously or transiently over certain periods of ontogenesis and in adulthood under functional insufficiency of the MA-ergic neurons, e.g., under their chronic stimulation or in certain neurodegenerative diseases. The earlier data suggest an important functional role of monoenzymatic neurons. Most monoenzymatic neurons possess enzymes of dopamine (DA) synthesis, tyrosine hydroxylase (TH), or aromatic l-amino acid decarboxylase (AADC). TH and AADC are enzymatically active in a substantial number of monoenzymatic neurons being capable to convert l-tyrosine to l-3,4-dihydroxyphenylalanine (l-DOPA) and L-DOPA to DA or serotonin, respectively. L-DOPA produced in monoenzymatic TH-neurons is supposed to play a role of a neurotransmitter or a neuromodulator providing its action on the target neurons via catecholamine receptors. Moreover, l-DOPA released from the monoenzymatic TH-neurons is captured by monoenzymatic AADC-neurons or dopaminergic (DA-ergic) and serotoninergic neurons for DA synthesis (Kannari et al., 2006). Such cooperative synthesis of MAs is considered as a compensatory reaction under the failure of MA-ergic neurons, e.g., in neurodegenerative diseases like hyperprolactinemia and Parkinson's disease which are developed primarily because of the degeneration of DA-ergic neurons of the tuberoinfundibular system and the nigrostriatal system, respectively. Noteworthy, the neurotoxin-induced increased level of prolactin returns with time to the normal level due to stimulation of DA synthesis by the neurons of the tuberoinfundibular system, most probably because of the turning on cooperative synthesis of DA by monoenzymatic neurons. The same compensatory mechanism is supposed to be used under the failure of the nigrostriatal DA-ergic system that is manifested by the increased number of monoenzymatic neurons in the striatum of animals with neurotoxin-induced parkinsonism and in humans with Parkinson's disease. Expression of the enzymes of MA synthesis in non-MA-ergic neurons is controlled by intercellular signals such as classical neurotransmitters (catecholamines), neurotrophic factors (brain-derived neurotrophic factor, glia-derived neurotrophic factor), and perhaps hormones (prolactin, estrogens, progesterone). Thus, a substantial number of the brain neurons express partly the MA-ergic phenotype, mostly individual complementary enzymes of MA synthesis, serving to produce MAs in cooperation that is considered as a compensatory reaction under the failure of MA-ergic neurons.02/2008: pages 21-73;
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ABSTRACT: The purpose of this study was to determine whether the increased expression of tyrosine hydroxylase (TH), the first and limiting enzyme in catecholamine synthesis in vasopressin (VP) neurons of the human neonate, represents a primary developmental phenomenon or reflects a secondary phenomenon related to the activation of VP systems due to perinatal hypoxia. Using immunohistochemistry, we investigated TH expression in the supraoptic nucleus (SON) of 15 human neonates at autopsy in relation to the age and severity/duration of hypoxic injury that was estimated on the basis of neuropathological criteria. Increased expression of TH was observed selectively in VP-synthesizing neurons of neonates who experienced prolonged perinatal hypoxia; was not related to the age, body weight/percentile, brain weight, or head perimeter of the subjects but depended on the neuropathological grade of the hypoxic injury (p < 0.01); and was found in VP-synthesizing neurons with increased cellular and nuclear size, that is, neurons with histological evidence of activation. Taken together, these observations indicate that increased expression of TH in VP neurons of SON is not developmentally determined but represents a response to hypoxic stress. We propose that increased TH expression in SON neurons of the human neonate may serve as a neuropathological marker of prolonged perinatal hypoxia in autopsy material.Journal of Neuropathology and Experimental Neurology 10/2010; 69(10):1008-16. · 4.37 Impact Factor