NDLI: Are Synchronized Changes in Connexin-43 and Caveolin-3 a Bystander Effect in a Phoneutria nigriventer Venom Model of Blood-Brain Barrier Breakdown?

Content Provider	Springer Nature Link
Author	Soares, Edilene Siqueira Mendonça, Monique Culturato Padilha Rocha, Thalita Kalapothakis, Evanguedes Cruz Höfling, Maria Alice
Copyright Year	2016
Abstract	Upregulation of caveolin-3 (Cav-3) or connexin-43 (Cx43) in astrocytes has been associated with important brain pathologies. We used Phoneutria nigriventer spider venom (PNV), which induces blood-brain barrier breakdown in rats, in order to investigate Cav-3 and Cx43 expression in the cerebellum over critical periods of rat envenomation. By immunofluorescence, western blotting (WB), and transmission electron microscopy (TEM), we assessed changes at 1, 2, 5, 24, and 72 h post-venom. WB showed immediate increases in Cav-3 and Cx43 at 1 h (interval of greatest manifestations of envenomation) that persisted at 5 h (when there were signs of recovery) and peaked at 24 h when no signs of envenomation were detectable. At 2 and 72 h, Cav-3 was downregulated and Cx43 had returned to baseline. PNV markedly intensified Cx43 in molecular, Purkinje and granular layers and Cav-3 in astrocytes whose colocalization to increased GFAP suggests interaction between reactive astrogliosis and Cav-3 upregulation. TEM showed swollen perivascular astrocytic end-feet and synaptic contact alterations that had generally resolved by 72 h. It is uncertain whether such PNV-induced synchronized changes are an interactive effect between Cav-3 and Cx43, or a bystander effect. Evidences indicate that Cav-3 downregulation coupled to Cx43 return to baseline at 72 h when no signs of envenomation were visible, suggesting homeostasis reestablishment. This experimental model is relevant to studying mechanisms involved in neurological disorders associated with Cav-3 overexpression.
Starting Page	452
Ending Page	463
Page Count	12
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	59
Issue Number	4
e-ISSN	15591166
Language	English
Publisher	Springer US
Publisher Date	2016-04-11
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Astrocytes Caveolin-3 Gap junctions Phoneutria nigriventer Ultrastructural changes Neurosciences Neurochemistry Cell Biology Proteomics Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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