Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria Nigriventer Spider Venom

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Nov 26

PMID 27886057

Citations 1

Authors

Edilene S Soares

Leila M Stavale

Monique C P Mendonca

Andressa Coope

Maria Alice da Cruz-Hofling

Affiliations

Soon will be listed here.

Abstract

We have previously demonstrated that venom (PNV) causes blood-brain barrier (BBB) breakdown, swelling of astrocytes end-feet and fluid permeation into brain interstitium in rats. Caveolae and water channels respond to BBB alterations by co-participation in shear stress response and edema formation/resolution. Herein, we showed post-natal developmental-related changes of two BBB-associated transporter proteins: the endothelial caveolin-1 (Cav-1), the major scaffolding protein from caveolae frame, and the astroglial aquaporin-4 (AQP4), the main water channel protein expressed in astrocytic peri-vascular end-feet processes, in the hippocampus of rats intraperitoneally-administered PNV. Western blotting protein levels; immunohistochemistry (IHC) protein distribution in CA1, CA2, and CA3 subfields; and gene expression by Real Time-Polymerase Chain Reaction (qPCR) were assessed in post-natal Day 14 (P14) and 8-10-week-old rats over critical periods of envenomation. The intensity and duration of the toxic manifestations indicate P14 neonate rats more vulnerable to PNV than adults. Histologically, the capillaries of P14 and 8-10-week-old rats treated with PNV showed perivascular edema, while controls did not. The intensity of the toxic manifestations in P14 decreases temporally (2 > 5 > 24 h), while inversely the expression of AQP4 and Cav-1 peaked at 24 h when clinically PNV-treated animals do not differ from saline controls. IHC of AQP4 revealed that hippocampal CA1 showed the least expression at 2 h when toxic manifestation was maximal. Subfield IHC quantification revealed that in P14 rats Cav-1 peaked at 24 h when toxic manifestations were absent, whereas in 8-10-week-old rats Cav-1 peaked at 2 h when toxic signs were highest, and progressively attenuated such increases until 24 h, remaining though significantly above baseline. Considering astrocyte-endothelial physical and functional interactions, we hypothesize that age-related modulations of AQP4 and Cav-1 might be linked both to changes in functional properties of astrocytes during post-natal development and in the BBB breakdown induced by the venom of .

Citing Articles

CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats.

Hua Q, Shen S, Qin Y, Cao S Pain Res Manag. 2022; 2022:8566840.

PMID: 35958678 PMC: 9357801. DOI: 10.1155/2022/8566840.

References

Nicchia G, Nico B, Camassa L, Mola M, Loh N, Dermietzel R . The role of aquaporin-4 in the blood-brain barrier development and integrity: studies in animal and cell culture models. Neuroscience. 2004; 129(4):935-45. DOI: 10.1016/j.neuroscience.2004.07.055. View

Raposo C, Zago G, da Silva G, Hofling M . Acute blood-brain barrier permeabilization in rats after systemic Phoneutria nigriventer venom. Brain Res. 2007; 1149:18-29. DOI: 10.1016/j.brainres.2007.02.086. View

Le Sueur L, Collares-Buzato C, da Cruz-Hofling M . Mechanisms involved in the blood-brain barrier increased permeability induced by Phoneutria nigriventer spider venom in rats. Brain Res. 2004; 1027(1-2):38-47. DOI: 10.1016/j.brainres.2004.08.055. View

Soares E, Mendonca M, da Cruz-Hofling M . eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom. Toxicon. 2015; 104:7-13. DOI: 10.1016/j.toxicon.2015.07.009. View

Nielsen S, Nagelhus E, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen O . Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci. 1997; 17(1):171-80. PMC: 6793699. View

Cruz-Hofling M, Love S, Brook G, DUCHEN L . Effects of Phoneutria nigriventer spider venom on mouse peripheral nerve. Q J Exp Physiol. 1985; 70(4):623-40. DOI: 10.1113/expphysiol.1985.sp002949. View

Hirota M, Moro O . MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line. Toxicol In Vitro. 2005; 20(5):736-42. DOI: 10.1016/j.tiv.2005.10.013. View

da Cruz-Hofling M, Zago G, Melo L, Raposo C . c-FOS and n-NOS reactive neurons in response to circulating Phoneutria nigriventer spider venom. Brain Res Bull. 2007; 73(1-3):114-26. DOI: 10.1016/j.brainresbull.2007.01.017. View

Silva F, Batista E, Gomez M, Kushmerick C, da Silva J, Cordeiro M . The Phoneutria nigriventer spider toxin, PnTx4-5-5, promotes neuronal survival by blocking NMDA receptors. Toxicon. 2016; 112:16-21. DOI: 10.1016/j.toxicon.2016.01.056. View

10.

Borgnia M, Nielsen S, Engel A, Agre P . Cellular and molecular biology of the aquaporin water channels. Annu Rev Biochem. 2000; 68:425-58. DOI: 10.1146/annurev.biochem.68.1.425. View

11.

Schnitzer J, Oh P, Pinney E, Allard J . Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J Cell Biol. 1994; 127(5):1217-32. PMC: 2120262. DOI: 10.1083/jcb.127.5.1217. View

12.

Bu J, Bruckner S, Sengoku T, Geddes J, Estus S . Glutamate regulates caveolin expression in rat hippocampal neurons. J Neurosci Res. 2003; 72(2):185-90. DOI: 10.1002/jnr.10556. View

13.

Binder D, Nagelhus E, Ottersen O . Aquaporin-4 and epilepsy. Glia. 2012; 60(8):1203-14. DOI: 10.1002/glia.22317. View

14.

de Paula Le Sueur L, Kalapothakis E, da Cruz-Hofling M . Breakdown of the blood-brain barrier and neuropathological changes induced by Phoneutria nigriventer spider venom. Acta Neuropathol. 2003; 105(2):125-34. DOI: 10.1007/s00401-002-0623-8. View

15.

Wen H, Nagelhus E, Amiry-Moghaddam M, Agre P, Ottersen O, Nielsen S . Ontogeny of water transport in rat brain: postnatal expression of the aquaporin-4 water channel. Eur J Neurosci. 1999; 11(3):935-45. DOI: 10.1046/j.1460-9568.1999.00502.x. View

16.

Verkman A, Binder D, Bloch O, Auguste K, Papadopoulos M . Three distinct roles of aquaporin-4 in brain function revealed by knockout mice. Biochim Biophys Acta. 2006; 1758(8):1085-93. DOI: 10.1016/j.bbamem.2006.02.018. View

17.

Santhanam A, Duscio L, Smith L, Katusic Z . Uncoupling of eNOS causes superoxide anion production and impairs NO signaling in the cerebral microvessels of hph-1 mice. J Neurochem. 2012; 122(6):1211-8. PMC: 3433644. DOI: 10.1111/j.1471-4159.2012.07872.x. View

18.

Nag S, Kapadia A, Stewart D . Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol. 2010; 37(1):3-23. DOI: 10.1111/j.1365-2990.2010.01138.x. View

19.

Fontana M . Mode of action of Phoneutria nigriventer spider venom at the isolated phrenic nerve-diaphragm of the rat. Braz J Med Biol Res. 1985; 18(4):557-65. View

20.

Ikezu T, Ueda H, Trapp B, Nishiyama K, Sha J, Volonte D . Affinity-purification and characterization of caveolins from the brain: differential expression of caveolin-1, -2, and -3 in brain endothelial and astroglial cell types. Brain Res. 1998; 804(2):177-92. DOI: 10.1016/s0006-8993(98)00498-3. View