Abstract
Acidic–alkaline stresses caused by ischemia and hypoglycemia induce neuronal cell death resulting from intracellular pH disturbance. The effects of acidic–alkaline disturbance on the trigeminal ganglion (TG) neurons of the embryonic mouse were investigated by caspase-3-immunohistochemistry and Nissl staining. TG neurons exhibited apoptosis in 3.08 ± 0.55% of neurons in intact embryos at day 16. Intraperitoneal injection of alkaline solution (pH 8.97; 0.005–0.1 M K2HPO4 or 0.01–0.04 M KOH) into the embryo at embryonic day 15 significantly increased the number of apoptotic neurons in the TG at embryonic day 16 with dependence on concentration (3.40–6.05 and 2.93–5.55%, respectively). On the other hand, acidic solutions (pH 4.4; 0.01–0.2 M KH2PO4) slightly, but not significantly, increased the number of apoptotic cells (3.64–5.15%, without dependence on concentration). Neutral solutions (pH 7.4; 0.01–0.2 M potassium phosphate buffer) had no effect on neuronal survival in the TG (2.89–3.48%). The results indicated that alkaline stress significantly increased apoptosis in the developing nervous system, but acidic stress did not.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Auer RN (2004) Hypoglycemic brain damage. Metab Brain Dis 19:169–175
Barde YA (1989) Trophic factors and neuronal survival. Neuron 2:1525–1534
Battaglia G, Bassanini S, Granata T, Setola V, Giavazzi A, Pagliardini S (2003) The genesis of epileptogenic cerebral heterotopia: clues from experimental models. Epileptic Disord 5(Suppl 2):S51–S58
Bortner CD, Hughes FM Jr, Cidlowski JA (1997) A primary role for K+ and Na+ efflux in the activation of apoptosis. J Biol Chem 272:32436–32442
Bouyer P, Bradley SR, Zhao J, Wang W, Richerson GB, Boron WF (2004) Effect of extracellular acid-base disturbances on the intracellular pH of neurones cultured from rat medullary raphe or hippocampus. J Physiol 559(Pt 1):85–101
Cattaneo E, Reinach B, Caputi A, Cattabeni F, Di Luca M (1995) Selective in vitro blockade of neuroepithelial cells proliferation by methylazoxymethanol, a molecule capable of inducing long lasting functional impairments. J Neurosci Res 41:640–647
Colacitti C, Sancini G, DeBiasi S, Franceschetti S, Caputi A, Frassoni C, Cattabeni F, Avanzini G, Spreafico R, Di Luca M, Battaglia G (1999) Prenatal methylazoxymethanol treatment in rats produces brain abnormalities with morphological similarities to human developmental brain dysgeneses. J Neuropathol Exp Neurol 58:92–106
Davies AM (1987) Molecular and cellular aspects of patterning sensory neurone connections in the vertebrate nervous system. Development 101:185–208
Ding D, Moskowitz SI, Li R, Lee SB, Esteban M, Tomaselli K, Chan J, Bergold PJ (2000) Acidosis induces necrosis and apoptosis of cultured hippocampal neurons. Exp Neurol 162:1–12
Emerit J, Edeas M, Bricaire F (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58:39–46
Franco-Cea A, Valencia A, Sánchez-Armass S, Domínguez G, Morán J (2004) Role of ionic fluxes in the apoptotic cell death of cultured cerebellar granule neurons. Neurochem Res 29:227–238
Fujita H, Ishizaki Y, Yanagisawa A, Morita I, Murota SI, Ishikawa K (1999) Possible involvement of a chloride-bicarbonate exchanger in apoptosis of endothelial cells and cardiomyocytes. Cell Biol Int 23:241–249
Giffard RG, Weiss JH, Choi DW (1992) Extracellular alkalinity exacerbates injury of cultured cortical neurons. Stroke 23:1817–1821
Hartley Z, Dubinsky JM (1993) Changes in intracellular pH associated with glutamate excitotoxicity. J Neurosci 13:4690–4699
Herberth B, Pataki A, Jelitai M, Schlett K, Deák F, Spät A, Madarász E (2002) Changes of KCl sensitivity of proliferating neural progenitors during in vitro neurogenesis. J Neurosci Res 67:574–582
Hughes FM Jr, Bortner CD, Purdy GD, Cidlowski JA (1997) Intracellular K+ suppresses the activation of apoptosis in lymphocytes. J Biol Chem 272:30567–30576
Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237:1154–1162
Mabe H, Blomqvist P, Siesjö BK (1983) Intracellular pH in the brain following transient ischemia. J Cereb Blood Flow Metab 3:109–114
Majima HJ, Oberley TD, Furukawa K, Mattson MP, Yen HC, Szweda LI, St Clair DK (1998) Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. J Biol Chem 273:8217–8224
Mathot M, Maton P, Henrion E, François-Adant A, Marguglio A, Gaillez S, Collard L, Langhendries JP (2006) Pseudo-Bartter syndrome in a pregnant mother and her fetus. Pediatr Nephrol 21:1037–1040
Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC (2000) Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nat Cell Biol 2:318–325
Ostermann ME, Girgis-Hanna Y, Nelson SR, Eastwood JB (2003) Metabolic alkalosis in patients with renal failure. Nephrol Dial Transpl 18:2442–2448
Pérez-Sala D, Collado-Escobar D, Mollinedo F (1995) Intracellular alkalinization suppresses lovastatin-induced apoptosis in HL-60 cells through the inactivation of a pH-dependent endonuclease. J Biol Chem 270:6235–6242
Rozance PJ, Crispo MM, Barry JS, O’Meara MC, Frost MS, Hansen KC, Hay WW Jr, Brown LD (2009) Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation. Am J Physiol Endocrinol Metab 297:E638–E646
Sadakata T, Washida M, Iwayama Y, Shoji S, Sato Y, Ohkura T, Katoh-Semba R, Nakajima M, Sekine Y, Tanaka M, Nakamura K, Iwata Y, Tsuchiya KJ, Mori N, Detera-Wadleigh SD, Ichikawa H, Itohara S, Yoshikawa T, Furuichi T (2007) Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest 117:931–943
Shimizu S, Ichikawa H, Nakagawa H, Kiyomiya K, Matsuo S (2007) Effect of BDNF deletion on the formation of Ruffini endings in vibrissa follicles and the survival of their mechanoreceptive neurons in trigeminal ganglion. Brain Res 1154:95–104
Shrode LD, Tapper H, Grinstein S (1997) Role of intracellular pH in proliferation, transformation, and apoptosis. J Bioenerg Biomembr 29:393–399
Trubiani G, Al Chawaf A, Belsham DD, Barsyte-Lovejoy D, Lovejoy DA (2007) Teneurin carboxy (C)-terminal associated peptide-1 inhibits alkalosis-associated necrotic neuronal death by stimulating superoxide dismutase and catalase activity in immortalized mouse hypothalamic cells. Brain Res 1176:27–36
Tsao N, Lei HY (1996) Activation of the Na(+)/H(+) antiporter, Na+/HCO3(−)/CO3(2−) cotransporter, or Cl(−)/HCO3(−) exchanger in spontaneous thymocyte apoptosis. J Immunol 157:1107–1116
Vincent AM, TenBroeke M, Maiese K (1999a) Metabotropic glutamate receptors prevent programmed cell death through the modulation of neuronal endonuclease activity and intracellular pH. Exp Neurol 155:79–94
Vincent AM, TenBroeke M, Maiese K (1999b) Neuronal intracellular pH directly mediates nitric oxide-induced programmed cell death. J Neurobiol 40:171–184
Voyame J, Terrier P, Guignard JP, Cachat F (1999) Transient hypokalemic metabolic alkalosis in a newborn mimicking Bartter’s syndrome. J Pediatr 134:794
Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LM, Farhangrazi ZS, Ying HS, Tian M, Dugan LL, Choi DW (1997) Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 278:114–117
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mukai, S., Nakagawa, H., Ichikawa, H. et al. Effects of extracellular acidic–alkaline stresses on trigeminal ganglion neurons in the mouse embryo in vivo. Arch Toxicol 85, 149–154 (2011). https://doi.org/10.1007/s00204-010-0556-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-010-0556-2