Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals

Wang, H; Wolosker, Herman; Pevsner, Jonathan; Snyder, S. H.; Selkoe, DJ

doi:10.1677/joe.0.1670247

Cited by 69 publications

(41 citation statements)

References 28 publications

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“…D-aspartate has been found in significant amounts in different nuclei of rat brain, particularly those engaged in neurosecretion (Schell et al, 1997, D'Aniello et al, 2000aWang et al, 2000). The highest concentrations have been observed in the rat pineal gland (Lee et al, 1997), and here the amino acid is proposed to modulate the synthesis of melatonin in pinealocytes (Ishio et al, 1998;Takigawa et al, 1998).…”

Section: Discussionmentioning

confidence: 97%

Cellular and subcellular distribution of D‐aspartate oxidase in human and rat brain

Zaar

Köst

Schad

et al. 2002

J of Comparative Neurology

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The unusual amino acid D-aspartate is present in significant amounts in brain and endocrine glands and is supposed to be involved in neurotransmission and neurosecretion (Wolosker et al. [2000] Neuroscience 100:183-189). D-aspartate oxidase is the only enzyme known to metabolize D-aspartate and could regulate its level in different regions of the brain. We examined the cellular and subcellular distribution of this enzyme and its mRNA in human and rat brain by immunohistochemistry, in situ hybridization, and immunoelectron microscopy. D-aspartate oxidase protein and mRNA are ubiquitous. The protein shows a granular pattern, particularly within neurons and to a significantly lesser extent in astrocytes and oligodendrocytes. No evidence for a synaptic association was observed. Whereas between most positive neurons only gradual differences were observed, in the hypothalamic paraventricular nucleus, neurons with high enzyme content were found next to others with no labeling. cDNA cloning of D-aspartate oxidase corroborates an inherent targeting signal sequence for protein import into peroxisomes. Immunoelectron microscopy showed that the protein is localized in single membrane-bound organelles, apparently peroxisomes.

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Section: Discussionmentioning

confidence: 97%

Cellular and subcellular distribution of D‐aspartate oxidase in human and rat brain

Zaar

Köst

Schad

et al. 2002

J of Comparative Neurology

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“…-Asp is the precursor for the synthesis of N-methyl-D-aspartic acid (NMDA) and the enzyme catalyzing this reaction is the N-methyl transferase, as reported in previous work carried out in rats (D'Aniello et al 2000a,b). -Asp is localized in various neurons of rat brain, including the hippocampus, and in the hypothalamo-neurohypophyseal system suggesting its involvement in regulating the neurosecretory system (Schell et al 1997, D'Aniello et al 2000a, Wang et al 2000. In vertebrates, this amino acid occurs in the nervous tissues of chickens (Neidle & Dunlop 1990), rats (Dunlop et al 1986, D'Aniello et al 1993, 2000a,b, Hashimoto et al 1993 and humans (Fisher et al 1991(Fisher et al , 1994).…”

Section: Introductionmentioning

confidence: 99%

Endocrine roles of d-aspartic acid in the testis of lizard Podarcis s. sicula

Raucci¹,

D’Aniello²,

Fiore³

2005

Journal of Endocrinology

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In the lizard Podarcis s. sicula, a substantial amount of -aspartate (-Asp) is endogenous to the testis and shows cyclic changes of activity connected with sex hormone profiles during the annual reproductive phases. Testicular -Asp content shows a direct correlation with testosterone titres and a reverse correlation with 17 -estradiol titres.In vivo experiments, consisting of i.p. injections of 2·0 µmol/g body weight of -Asp or other amino acids, in lizards collected during the three main phases of the reproductive cycle (pre-reproductive, reproductive and post-reproductive period), revealed that the testis can specifically take up and accumulate -Asp alone. Moreover, this amino acid influences the synthesis of testosterone and 17 -estradiol in all phases of the cycle. This phenomenon is particularly evident during the pre-and post-reproductive period, when endogenous testosterone levels observed in both testis and plasma were the lowest and 17 -estradiol concentrations were the highest. -Asp rapidly induces a fall in 17 -estradiol and a rise in testosterone at 3 h post-injection in the testis and at 6 h post-injection in the blood. In vitro experiments show that testicular tissue converted -Asp into -Asp through an aspartate racemase. -Asp synthesis was measured in all phases of the cycle, but was significantly higher during the reproductive period with a peak at pH 6·0. The exogenous -Asp also induces a significant increase in the mitotic activity of the testis at 3 h (P<0·05) and at 6 h (P<0·01). Induction of spermatogenesis by -Asp is recognized by an intense immunoreactivity of the germinal epithelium (spermatogonia and spermatids) for proliferation cell nuclear antigen (PCNA). The effects of -Asp on the testis appear to be specific since they were not seen in lizards injected with other -or -forms of amino acids with known excitatory effects on neurosecretion. Our results suggest a regulatory role for -Asp in the steroidogenesis and spermatogenesis of the testis of the lizard Podarcis s. sicula.

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“…Most recent investigations have concerned the nervous and endocrine system of mammals, including humans (Dunlop et al 1986, Fisher et al 1991, Hashimoto et al 1993, Hashimoto & Oka 1997, D'Aniello et al 1998a, where -Asp is well represented. In the nervous system, -Asp is now accepted as one of the numerous agents involved in neurotransmission and neurosecretion (Schell et al 1997); it is, in fact, localized in different nuclei of rat brain (Wang et al 2002), particularly those engaged in neurosecretion (Schell et al 1997, D'Aniello et al 2000a, Wang et al 2000.…”

Section: Introductionmentioning

confidence: 99%

“…The highest concentrations of -Asp have been observed in the rat pineal gland (Imai et al 1995, Lee et al 1997, and here the amino acid modulates the secretion (Takigawa et al 1998) and synthesis (Ishio et al 1998) of melatonin in pinealocytes. Furthermore, -Asp is thought to stimulate hormone production in rat hypothalamic nuclei, as well as hormone production and secretion in the rat adeno-(D' Aniello et al 2000a,b) and neuro-hypophysis (Wang et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Testicular endocrine activity is upregulated by D-aspartic acid in the green frog, Rana esculenta

Raucci¹,

Assisi²,

D’Aniello³

et al. 2004

Journal of Endocrinology

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This study investigated the involvement of -aspartic acid (-Asp) in testicular steroidogenesis of the green frog Rana esculenta and its effect on stimulation of thumb pad morphology and glandular activity, a typical testosteronedependent secondary sexual characteristic in this amphibian species. In the testis, -Asp concentrations vary significantly during the reproductive cycle: they are low in pre-and post-reproductive periods, but reach peak levels in the reproductive period (140-236 nmol/g wet tissue). Moreover, the concentrations of -Asp in the testis through the sexual cycle positively match the testosterone levels in the gonad and the plasma. The racemase activity evaluated during the cycle expresses its peak when -Asp and testosterone levels are highest, that is, during the reproductive period, confirming the synthesis of -Asp from -Asp by an aspartate racemase. Short-term in vivo experiments consisting of a single injection of -Asp (2·0 µmol/g body weight) demonstrated that this amino acid accumulates significantly in the testis, and after 3 h its uptake is coupled with a testosterone increase in both testis and plasma. Moreover, within 18 h of amino acid administration, the -Asp concentration in the testis decreased along with the testosterone titer to prestimulation levels. Other amino acids (-Asp, -Glu and -Glu) used instead of -Asp were ineffective, confirming that the significant increase in testicular testosterone was a specific feature of this amino acid. In long-term experiments, -Asp had been administered chronically to frogs caught during the three phases of the reproductive cycle, inducing testosterone increase and 17 -estradiol decrease in the gonad during the pre-and post-reproductive period, and vice versa during the reproductive period.The stimulatory effect of -Asp on testosterone production by the testis is consistent with the stimulation of spermatogenesis and the maturation of thumb pads occurring in -Asp-treated frogs. In these last animals, there was an increase of seminiferous ampoule area and a higher number of spermatids and sperm. Moreover, in spermatogonia I and II and in spermatocytes, a proliferating cell nuclear antigen (PCNA) intense immunopositivity was observed. In addition, the thumb pads of -Asptreated frogs compared with controls showed a significantly thicker epithelial lining, a wider area of their glands with taller secretion cells, and more numerous, PASpositive-rich secretions. Finally, these results provide functional evidence for a biologic role of -Asp in amphibian male steroidogenesis; therefore, this unusual amino acid could be considered a modulatory agent for reproductive processes.

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Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals

Cited by 69 publications

References 28 publications

Cellular and subcellular distribution of D‐aspartate oxidase in human and rat brain

Cellular and subcellular distribution of D‐aspartate oxidase in human and rat brain

Endocrine roles of d-aspartic acid in the testis of lizard Podarcis s. sicula

Testicular endocrine activity is upregulated by D-aspartic acid in the green frog, Rana esculenta

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