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Modification of purinergic signaling in the hippocampus of streptozotocin-induced diabetic rats

Duarte, J. M.N. LU orcid ; Oses, J. P. ; Rodrigues, R. J. and Cunha, R. A. (2007) In Neuroscience 149(2). p.382-391
Abstract

Diabetic encephalopathy is a recognized complication of untreated diabetes resulting in a progressive cognitive impairment accompanied by modification of hippocampal function. The purinergic system is a promising novel target to control diabetic encephalopathy since it might simultaneously control hippocampal synaptic plasticity and glucose handling. We now tested whether streptozotocin-induced diabetes led to a modification of extracellular ATP homeostasis and density of membrane ATP (P2) receptors in the hippocampus, a brain structure involved in learning and memory. The extracellular levels of ATP, evaluated in the cerebrospinal fluid, were reduced by 60.4±17.0% in diabetic rats. Likewise, the evoked release of ATP as well as its... (More)

Diabetic encephalopathy is a recognized complication of untreated diabetes resulting in a progressive cognitive impairment accompanied by modification of hippocampal function. The purinergic system is a promising novel target to control diabetic encephalopathy since it might simultaneously control hippocampal synaptic plasticity and glucose handling. We now tested whether streptozotocin-induced diabetes led to a modification of extracellular ATP homeostasis and density of membrane ATP (P2) receptors in the hippocampus, a brain structure involved in learning and memory. The extracellular levels of ATP, evaluated in the cerebrospinal fluid, were reduced by 60.4±17.0% in diabetic rats. Likewise, the evoked release of ATP as well as its extracellular catabolism was also decreased in hippocampal nerve terminals of diabetic rats by 52.8±10.9% and 38.7±6.5%, respectively. Western blot analysis showed that the density of several P2 receptors (P2X3,5,7 and P2Y2,6,11) was decreased in hippocampal nerve terminals. This indicates that the synaptic ATP signaling is globally depressed in diabetic rats, which may contribute for diabetes-associated decrease of synaptic plasticity. In contrast, the density of P2 receptors (P2X1,2,5,6,7 and P2Y6 but not P2Y2) increased in whole hippocampal membranes, suggesting an adaptation of non-synaptic P2 receptors to sense decreased levels of extracellular ATP in diabetic rats, which might be aimed at preserving the non-synaptic purinergic signaling.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATP, diabetes, ecto-nucleotidases, hippocampus, P2 receptors, streptozotocin
in
Neuroscience
volume
149
issue
2
pages
382 - 391
publisher
Elsevier
external identifiers
  • pmid:17869435
  • scopus:35348895686
ISSN
0306-4522
DOI
10.1016/j.neuroscience.2007.08.005
language
English
LU publication?
no
additional info
Funding Information: This work was supported by Fundação para a Ciência e a Tecnologia (FCT, grant POCTI/SAU-NEU/56098/2004) and by Fundo Fundação Oriente/Johnson & Johnson Para a Saúde. João M. N. Duarte acknowledges a PhD grant from FCT (SFRH/BD/17795/2004). Jean Pierre Oses acknowledges a PhD grant from CNPq/Brasil (200127/2005-5).
id
7a29a58f-d3ad-4319-a994-f874b4b3f223
date added to LUP
2024-01-08 10:55:47
date last changed
2024-04-23 06:32:54
@article{7a29a58f-d3ad-4319-a994-f874b4b3f223,
  abstract     = {{<p>Diabetic encephalopathy is a recognized complication of untreated diabetes resulting in a progressive cognitive impairment accompanied by modification of hippocampal function. The purinergic system is a promising novel target to control diabetic encephalopathy since it might simultaneously control hippocampal synaptic plasticity and glucose handling. We now tested whether streptozotocin-induced diabetes led to a modification of extracellular ATP homeostasis and density of membrane ATP (P2) receptors in the hippocampus, a brain structure involved in learning and memory. The extracellular levels of ATP, evaluated in the cerebrospinal fluid, were reduced by 60.4±17.0% in diabetic rats. Likewise, the evoked release of ATP as well as its extracellular catabolism was also decreased in hippocampal nerve terminals of diabetic rats by 52.8±10.9% and 38.7±6.5%, respectively. Western blot analysis showed that the density of several P2 receptors (P2X<sub>3,5,7</sub> and P2Y<sub>2,6,11</sub>) was decreased in hippocampal nerve terminals. This indicates that the synaptic ATP signaling is globally depressed in diabetic rats, which may contribute for diabetes-associated decrease of synaptic plasticity. In contrast, the density of P2 receptors (P2X<sub>1,2,5,6,7</sub> and P2Y<sub>6</sub> but not P2Y<sub>2</sub>) increased in whole hippocampal membranes, suggesting an adaptation of non-synaptic P2 receptors to sense decreased levels of extracellular ATP in diabetic rats, which might be aimed at preserving the non-synaptic purinergic signaling.</p>}},
  author       = {{Duarte, J. M.N. and Oses, J. P. and Rodrigues, R. J. and Cunha, R. A.}},
  issn         = {{0306-4522}},
  keywords     = {{ATP; diabetes; ecto-nucleotidases; hippocampus; P2 receptors; streptozotocin}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{2}},
  pages        = {{382--391}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience}},
  title        = {{Modification of purinergic signaling in the hippocampus of streptozotocin-induced diabetic rats}},
  url          = {{http://dx.doi.org/10.1016/j.neuroscience.2007.08.005}},
  doi          = {{10.1016/j.neuroscience.2007.08.005}},
  volume       = {{149}},
  year         = {{2007}},
}