Transient domoic acid excitotoxicity increases BDNF expression and activates both MEK- and PKA-dependent neurogenesis in organotypic hippocampal slices

Pérez-Gómez, Anabel; Tasker, R. Andrew

doi:10.1186/1471-2202-14-72

Cited by 24 publications

(8 citation statements)

References 98 publications

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“…One such neurotrophin is BDNF [ 37 , 38 ]. Traditionally, BDNF has been used as a marker for activation of intracellular cascades that regulate neuroplasticity, synaptogenesis and neurogenesis [ 22 , 39 – 43 ]. Furthermore, BDNF is linked with essential executive cognitive functions such as memory [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

et al. 2018

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In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9–11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage.

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Section: Discussionmentioning

confidence: 99%

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

et al. 2018

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“…The lack of effect of CIE on hippocampal tTrkB is consistent with other models of alcohol administration, such as two-bottle choice exposure (Briones and Woods 2013) and liquid diet (Zhang et al 2000). Importantly, the increased pTrkB-706 could indicate a BDNF-mediated enhanced TrkB activation, which is linked to hyperglutamatergic activity in the hippocampus (Marini et al 1998; Perez-Gomez and Tasker 2013). Since, hippocampal neuronal activity positively and bi-directionally interacts with hippocampal neurogenesis (van Praag et al 1999; Derrick et al 2000; Snyder et al 2001; Farmer et al 2004; Chun et al 2006, 2009), this hyperglutamatergic activity may also contribute to the early proliferative effects of CIE withdrawal (Mandyam 2013).…”

Section: Discussionmentioning

confidence: 99%

Alcohol dependence-induced regulation of the proliferation and survival of adult brain progenitors is associated with altered BDNF-TrkB signaling

et al. 2015

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Effects of withdrawal from ethanol drinking in chronic intermittent ethanol vapor (CIE)-exposed dependent rats and air-exposed nondependent rats on proliferation and survival of progenitor cells in the hippocampus and the medial prefrontal cortex (mPFC) were investigated. Rats were injected with 5′-Bromo 2-deoxyuridine 72 h post-CIE to measure proliferation (2 h-old cells) and survival (29-day-old cells) of progenitors born during a time-point previously reported to elicit a proliferative burst in the hippocampus. Hippocampal and mPFC brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B receptor (TrkB) expression were measured 3 h or 21d post-CIE to evaluate neurotrophic signaling during a time point preceding the proliferative burst and survival of newly born progenitors. CIE rats demonstrated elevated drinking compared to nondependent rats and CIE rats maintained elevated drinking following protracted abstinence. Withdrawal from CIE increased BDNF levels in the hippocampus and mPFC, and subsequently increased proliferation in the hippocampus and mPFC compared to nondependent rats and controls. Protracted abstinence from CIE reduced BDNF expression to control levels, and subsequently reduced neurogenesis compared to controls and nondependent rats in the hippocampus. In the mPFC, protracted abstinence reduced BDNF expression to control levels, whereas increased oligodendrogenesis in dependent rats compared to nondependent rats and controls. These results suggest a novel relationship between BDNF and progenitors in the hippocampus and mPFC, in which increased ethanol drinking may alter hippocampal and cortical function in alcohol dependent subjects by altering the cellular composition of newly born progenitors in the hippocampus and mPFC.

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“…Blocking this depolarizing but shunting GABA A transmission likely increased activity in our preparation, suggesting that the increase in glutamatergic synapses following GABA Ablockade at 3 DIV was driven by activity-dependent mechanisms (Balkowiec and Katz, 2002;Pérez-Gómez and Tasker, 2013). To begin to address this possibility, we measured levels of Bdnf and Fos mRNA, two activity-regulated genes associated with glutamatergic synapse formation (Vicario-Abejón et al, 1998, 2002Tyler and Pozzo-Miller, 2003;Chapleau et al, 2009).…”

Section: An Increase In Glutamatergic Synapses Following Blockade Of mentioning

confidence: 99%

Depolarizing GABA Transmission Restrains Activity-Dependent Glutamatergic Synapse Formation in the Developing Hippocampal Circuit

Salmon

Pribiag

Gizowski

et al. 2020

Front. Cell. Neurosci.

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γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mature brain but has the paradoxical property of depolarizing neurons during early development. Depolarization provided by GABA A transmission during this early phase regulates neural stem cell proliferation, neural migration, neurite outgrowth, synapse formation, and circuit refinement, making GABA a key factor in neural circuit development. Importantly, depending on the context, depolarizing GABA A transmission can either drive neural activity or inhibit it through shunting inhibition. The varying roles of depolarizing GABA A transmission during development, and its ability to both drive and inhibit neural activity, makes it a difficult developmental cue to study. This is particularly true in the later stages of development when the majority of synapses form and GABA A transmission switches from depolarizing to hyperpolarizing. Here, we addressed the importance of depolarizing but inhibitory (or shunting) GABA A transmission in glutamatergic synapse formation in hippocampal CA1 pyramidal neurons. We first showed that the developmental depolarizing-to-hyperpolarizing switch in GABA A transmission is recapitulated in organotypic hippocampal slice cultures. Based on the expression profile of K + −Cl − co-transporter 2 (KCC2) and changes in the GABA reversal potential, we pinpointed the timing of the switch from depolarizing to hyperpolarizing GABA A transmission in CA1 neurons. We found that blocking depolarizing but shunting GABA A transmission increased excitatory synapse number and strength, indicating that depolarizing GABA A transmission can restrain glutamatergic synapse formation. The increase in glutamatergic synapses was activity-dependent but independent of BDNF signaling. Importantly, the elevated number of synapses was stable for more than a week after GABA A inhibitors were washed out. Together these findings point to the ability of immature GABAergic transmission to restrain glutamatergic synapse formation and suggest an unexpected role for depolarizing GABA A transmission in shaping excitatory connectivity during neural circuit development.

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Transient domoic acid excitotoxicity increases BDNF expression and activates both MEK- and PKA-dependent neurogenesis in organotypic hippocampal slices

Cited by 24 publications

References 98 publications

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

Alcohol dependence-induced regulation of the proliferation and survival of adult brain progenitors is associated with altered BDNF-TrkB signaling

Depolarizing GABA Transmission Restrains Activity-Dependent Glutamatergic Synapse Formation in the Developing Hippocampal Circuit

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