Generation of specific antisera directed against D-amino acids: focus on the neuroanatomical distribution of D-glutamate and other D-amino acids
Abstract
This review updates the findings about the anatomical distribution (using immunohistochemical techniques) and possible functions of D-glutamate in the central nervous system of mammals, as well as compares the distribution of D-glutamate with the distribution of the most studied D-amino acids: D-serine and D-aspartate. The protocol used to obtain highly specific antisera directed against D-amino acids is also reported. Immunoreactivity for D-glutamate was found in dendrites and cell bodies, but not in nerve fibers. Perikarya containing D-glutamate were found in the mesencephalon and thalamus. The highest density of cell bodies was found in the dorsal raphe nucleus, the mesencephalic central grey matter, the superior colliculus, and in the subparafascicular thalamic nucleus. In comparison with the distribution of immunoreactive cell bodies containing D-serine or D-aspartate, the distribution of D-glutamate-immunoreactive perikarya is less widespread. Currently, the physiological actions mediated by D-glutamate in the brain are unknown but the restricted neuroanatomical distribution of this D-amino acid suggests that D-glutamate could be involved in very specific physiological mechanisms. In this sense, the possible functional roles of D-glutamate are discussed.
Keywords: antiseraD-aspartateD-glutamateD-glutamic acidD-serineIHCbrainratmapping
References
- Hamase K, Morikawa A, Zaitsu K. D-Amino acids in mammals and their diagnostic value. J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 781(1-2): 73–91.
- Hamase K, Morikawa A, Etoh S, et al. Analysis of small amounts of D-amino acids and the study of their physiological functions in mammals. Anal Sci. 2009; 25(8): 961–968.
- Genchi G. An overview on D-amino acids. Amino Acids. 2017 [Epub ahead of print].
- Mothet JP, Snyder SH. Brain D-amino acids: a novel class of neuromodulators. Amino Acids. 2012; 43(5): 1809–1810.
- Ohide H, Miyoshi Y, Maruyama R, et al. D-Amino acid metabolism in mammals: biosynthesis, degradation and analytical aspects of the metabolic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2011; 879(29): 3162–3168.
- Kiriyama Y, Nochi H. D-Amino Acids in the Nervous and Endocrine Systems. Scientifica (Cairo). 2016; 2016: 6494621.
- Lin CH, Yang HT, Chiu CC, et al. Blood levels of D-amino acid oxidase vs. D-amino acids in reflecting cognitive aging. Sci Rep. 2017; 7(1): 14849.
- Mothet J-s, Coveñas R, Geffard M. eds. Brain Molecules: from Vitamins to Molecules for Axonal Guidance. Trivandrum: Transworld Research Network. ; 2008: 105–129.
- Errico F, Napolitano F, Nisticò R, et al. New insights on the role of free D-aspartate in the mammalian brain. Amino Acids. 2012; 43(5): 1861–1871.
- Fuchs SA, Berger R, Klomp LWJ, et al. D-amino acids in the central nervous system in health and disease. Mol Genet Metab. 2005; 85(3): 168–180.
- Gozzi A, Herdon H, Schwarz A, et al. Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat. Psychopharmacology (Berl). 2008; 201(2): 273–284.
- Tsai G, Yang P, Chung LC, et al. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998; 44(11): 1081–1089.
- Ryu HJ, Kim JE, Yeo SI, et al. Potential roles of D-serine and serine racemase in experimental temporal lobe epilepsy. J Neurosci Res. 2010; 88(11): 2469–2482.
- Ishiwata S, Umino A, Nishikawa T. Involvement of neuronal and glial activities in control of the extracellular d-serine concentrations by the AMPA glutamate receptor in the mouse medial prefrontal cortex. Neurochem Int. 2017 [Epub ahead of print].
- Li Z, Xing Y, Guo X, et al. Development of an UPLC-MS/MS method for simultaneous quantitation of 11 d-amino acids in different regions of rat brain: Application to a study on the associations of d-amino acid concentration changes and Alzheimer's disease. J Chromatogr B Analyt Technol Biomed Life Sci. 2017; 1058: 40–46.
- Bardaweel SK, Alzweiri M, Ishaqat AA. D-Serine in neurobiology: CNS neurotransmission and neuromodulation. Can J Neurol Sci. 2014; 41(2): 164–176.
- Xia J, Xiong H. Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible involvement of D-serine. Int J Physiol Pathophysiol Pharmacol 2013; 5: 137-147. .
- Paul P, de Belleroche J. The role of D-amino acids in amyotrophic lateral sclerosis pathogenesis: a review. Amino Acids. 2012; 43(5): 1823–1831.
- Billard JM. D-Amino acids in brain neurotransmission and synaptic plasticity. Amino Acids. 2012; 43(5): 1851–1860.
- Takigawa Y, Homma H, Lee JA, et al. D-aspartate uptake into cultured rat pinealocytes and the concomitant effect on L-aspartate levels and melatonin secretion. Biochem Biophys Res Commun. 1998; 248(3): 641–647.
- Neidle A, Dunlop DS. Developmental changes in free D-aspartic acid in the chicken embryo and in the neonatal rat. Life Sci. 1990; 46(21): 1517–1522.
- Wang H, Wolosker H, Pevsner J, et al. Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals. J Endocrinol. 2000; 167(2): 247–252.
- Palazzo E, Luongo L, Guida F, et al. D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice. Amino Acids. 2016; 48(7): 1553–1567.
- Errico F, Di Maio A, Marsili V, et al. Bimodal effect of D-aspartate on brain aging processes: insights from animal models. J Biol Regul Homeost Agents. 2013; 27(2 Suppl): 49–59.
- Punzo D, Errico F, Cristino L, et al. Age-Related Changes in D-Aspartate Oxidase Promoter Methylation Control Extracellular D-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging. J Neurosci. 2016; 36(10): 3064–3078.
- Santillo A, Pinelli C, Burrone L, et al. Induced synthesis of P450 aromatase and 17β-estradiol by D-aspartate in frog brain. J Exp Biol. 2012; 215(Pt 20): 3559–3565.
- Nuzzo T, Sacchi S, Errico F, et al. Decreased free d-aspartate levels are linked to enhanced d-aspartate oxidase activity in the dorsolateral prefrontal cortex of schizophrenia patients. NPJ Schizophr. 2017; 3: 16.
- de Bartolomeis A, Errico F, Aceto G, et al. D-aspartate dysregulation in Ddo(-/-) mice modulates phencyclidine-induced gene expression changes of postsynaptic density molecules in cortex and striatum. Prog Neuropsychopharmacol Biol Psychiatry. 2015; 62: 35–43.
- Raj D, Langford M, Krueger S, et al. Regulatory responses to an oral D-glutamate load: formation of D-pyrrolidone carboxylic acid in humans. Am J Physiol Endocrinol Metab. 2001; 280(2): E214–E220.
- Pan ZZ, Tong G, Jahr CE. A false transmitter at excitatory synapses. Neuron. 1993; 11(1): 85–91.
- Fisher G, Petrucelli L, Gardner C, et al. Freed-amino acids in human cerebrospinal fluid of alzheimer disease, multiple sclerosis, and healthy control subjects. Molecular and Chemical Neuropathology. 1994; 23(2-3): 115–124.
- Yoshimura T, Esak N. Amino acid racemases: functions and mechanisms. J Biosci Bioeng. 2003; 96(2): 103–109.
- Smith SM, Uslaner JM, Hutson PH. The Therapeutic Potential of D-Amino Acid Oxidase (DAAO) Inhibitors. Open Med Chem J. 2010; 4: 3–9.
- Weatherly CA, Du S, Parpia C, et al. d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study. ACS Chem Neurosci. 2017; 8(6): 1251–1261.
- Karakawa S, Shimbo K, Yamada N, et al. Simultaneous analysis of D-alanine, D-aspartic acid, and D-serine using chiral high-performance liquid chromatography-tandem mass spectrometry and its application to the rat plasma and tissues. J Pharm Biomed Anal. 2015; 115: 123–129.
- Han H, Miyoshi Y, Koga R, et al. Changes in D-aspartic acid and D-glutamic acid levels in the tissues and physiological fluids of mice with various D-aspartate oxidase activities. J Pharm Biomed Anal. 2015; 116: 47–52.
- Miyoshi Y, Koga R, Oyama T, et al. HPLC analysis of naturally occurring free D-amino acids in mammals. J Pharm Biomed Anal. 2012; 69: 42–49.
- Kera Y, Aoyama H, Matsumura H, et al. Presence of free D-glutamate and D-aspartate in rat tissues. Biochim Biophys Acta. 1995; 1243(2): 283–286.
- Song Y, Feng Y, Lu X, et al. D-Amino acids in rat brain measured by liquid chromatography/tandem mass spectrometry. Neurosci Lett. 2008; 445(1): 53–57.
- Yasuda E, Ma N, Semba R. Immunohistochemical evidences for localization and production of D-serine in some neurons in the rat brain. Neurosci Lett. 2001; 299(1-2): 162–164.
- Puyal J, Martineau M, Mothet JP, et al. Changes in D-serine levels and localization during postnatal development of the rat vestibular nuclei. J Comp Neurol. 2006; 497(4): 610–621.
- Williams SM, Diaz CM, Macnab LT, et al. Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons. Glia. 2006; 53(4): 401–411.
- Liu YH, Wang L, Wei LC, et al. Up-regulation of D-serine might induce GABAergic neuronal degeneration in the cerebral cortex and hippocampus in the mouse pilocarpine model of epilepsy. Neurochem Res. 2009; 34(7): 1209–1218.
- Mangas A, Coveñas R, Bodet D, et al. Immunocytochemical visualization of D-glutamate in the rat brain. Neuroscience. 2007; 144(2): 654–664.
- Ding X, Ma N, Nagahama M, et al. Localization of D-serine and serine racemase in neurons and neuroglias in mouse brain. Neurol Sci. 2011; 32(2): 263–267.
- Mangas A, Coveñas R, Coveñas R, et al. et al.. Bodet D Antisera and immunocytochemical techniques. In: Mangas A, Coveñas R, Geffard M, eds. Brain Molecules: from Vitamins to Molecules for Axonal Guidance. Trivandrum: Transworld Research Network. ; 2008: 1–25.
- Mangas A, Yajeya J, Gonzalez N, et al. Detection of pantothenic acid-immunoreactive neurons in the rat lateral septal nucleus by a newly developed antibody. Folia Histochem Cytobiol. 2016; 54(4): 186–192.
- Chagnaud JL, Campistron G, Geffard M. Monoclonal antibody directed against glutaraldehyde conjugated glutamate and immunocytochemical applications in the rat brain. Brain Research. 1989; 481(1): 175–180.
- Pow DV, Crook DK. Direct immunocytochemical evidence for the transfer of glutamine from glial cells to neurons: use of specific antibodies directed against the d-stereoisomers of glutamate and glutamine. Neuroscience. 1996; 70(1): 295–302.
- León MDe, Coveñas R, Narváez JA, et al. Somatostatin-28 (1–12)-like immunoreactivity in the cat diencephalon. Neuropeptides. 1991; 19(2): 107–117.
- Schell MJ, Cooper OB, Snyder SH. D-aspartate localizations imply neuronal and neuroendocrine roles. Proc Natl Acad Sci U S A. 1997; 94(5): 2013–2018.
- Errico F, Napolitano F, Squillace M, et al. Decreased levels of D-aspartate and NMDA in the prefrontal cortex and striatum of patients with schizophrenia. J Psychiatr Res. 2013; 47(10): 1432–1437.
- Lecourtier L, Kelly PH. A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition. Neurosci Biobehav Rev. 2007; 31(5): 658–672.
- Hikosaka O, Sesack SR, Lecourtier L, et al. Habenula: crossroad between the basal ganglia and the limbic system. J Neurosci. 2008; 28(46): 11825–11829.
- Guilding C, Hughes ATL, Piggins HD. Circadian oscillators in the epithalamus. Neuroscience. 2010; 169(4): 1630–1639.
![](https://journals.viamedica.pl/plugins/generic/popups/images/icons/close.png)