• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • Caffeine decreased EAAT and EAAT


    Caffeine decreased EAAT1 and EAAT2 Vilazodone Hydrochloride sale levels in P2 fraction, as well as [3H]d-aspartate uptake; however, as soon as caffeine is removed from incubation, [3H]-d-Aspartate uptake is recovered to control levels, eliminating the possibility of caffeine as a cell death inducer. In resume, our data suggest that caffeine blocks adenosine A2A receptors, since addition of A2AR-specific antagonists (SCH58261 and ZM241385) inhibited [3H]-d-Aspartate uptake in immature retinas. Caffeine (after a 10min addition) induces [3H]d-aspartate release via NMDAR activation. Interestingly, inhibition of [3H]d-aspartate uptake promoted by caffeine is only seen after 60min. Therefore, actions of caffeine on [3H]d-aspartate uptake and release occur at different time points. Based on that, we hypothesize that in a first moment, caffeine could lead to the release of [3H]d-aspartate, which in turn, stimulates NMDARs with a consequent increase in total EAAT3 expression. Later, EAAT1 are reduced in the membranes of glial cells, thus inhibiting [3H]d-aspartate uptake.
    Conclusion A2AR are present in the immature rat retina regulating extracellular glutamate/aspartate concentrations below critical levels during tissue differentiation. Blocking of A2AR using caffeine, ZM241385 or SCH58261 reduce[3H]-d-aspartate uptake and as a consequence, might increase retina cellular excitability.
    Role of the funding source Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Brazil to RCCK. INNT-INCT.
    Conflict of interest
    Introduction Temporal lobe epilepsy (TLE) is one of the most common types of partial epilepsy [1]. This type of epilepsy may develop following an initial brain-damaging insult, and it is often resistant to antiepileptic drugs. Therefore, the prevention of epileptogenesis after a primary event could be a key innovative approach to TLE treatment. Unfortunately, the lack of clear data on the pathophysiological mechanisms leading to TLE does not allow any rational therapy [2]. The time points for epileptogenesis after an initial insult may be important clinically because these periods could be the critical time windows for protective or antiepileptogenic treatment to prevent the development of seizures [3]. Therefore, it is essential to understand the molecular and cellular mechanisms of epileptogenesis in detail. Animal models of TLE have been instrumental in clarifying the pathophysiology of epilepsy. The pilocarpine model of TLE belongs to a group of animal models that replicate the general progression of events as observed in humans [4], and this model has been used in many laboratories since its first description [5]. In this model, the injection of the convulsant pilocarpine induces status epilepticus (SE), likely through the activation of the M1 muscarinic receptor subtype [6], followed by a seizure-free latent period (1–6 weeks) and, eventually, the appearance of recurrent seizures that continue for the rest of the rat’s life [7]. It is believed that during the latent period, several pathophysiological phenomena that are related to epileptogenesis may occur. A growing body of evidence from the study of animal models suggests that alterations in excitatory neurotransmission play a central role in the pathogenesis of epilepsy, with the overstimulation of glutamate receptors potentially influencing the initiation, propagation, and maintenance of epileptic activity [8,9]. The recurrent seizures change the subunit composition and functional properties of AMPA and NMDA receptors [[10], [11], [12], [13], [14]]. AMPA receptors are formed as tetramers from combinations of the GluA1, GluA2, GluA3, and GluA4 subunits [15]. GluA2 subunits have been shown to play a particularly crucial role in the functional properties of heteromeric AMPARs. Channels consisting only of GluA1, GluA3, and GluA4 subunits display a strong, inwardly rectifying current-voltage relationship and calcium permeability, whereas the presence of GluA2 subunits excludes calcium permeability and inward rectification [16]. NMDA receptors exist as multiple subtypes with distinct Vilazodone Hydrochloride sale pharmacological and biophysical properties, which are mainly determined by the type of GluN2 subunit (GluN2a-GluN2d) incorporated into the heteromeric GluN1/GluN2 complex [15,17]. Perturbations in the brain’s glutamate-glutamine cycle, such as increased extracellular levels of glutamate, the loss of astroglial glutamine synthetase, and changes in excitatory amino acid transporters (EAATs) are frequently encountered in patients with epilepsy [18,19].