Loss of Long-Term Potentiation at Hippocampal Output Synapses in Experimental Temporal Lobe Epilepsy.

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation.

Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer's disease-like APPPS1 mice.

The immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the outcome of various diseases. In Alzheimer's disease (AD)-like APPPS1 mice Aβ-deposition is paralleled by iP upregulation, most likely mediated through type I interferon induction. To define the impact of increased iP expression we crossed APPPS1 mice with mice deficient in the iP subunit LMP7 resulting in impaired iP function.

TCF11/Nrf1-Mediated Induction of Proteasome Expression Prevents Cytotoxicity by Rotenone.

Aims: Precise regulation of cellular protein degradation is essential for maintaining protein and redox homeostasis. The ubiquitin proteasome system (UPS) represents one of the major degradation machineries, and UPS disturbances are strongly associated with neurodegeneration. We have previously shown that the transcription factor TCF11/Nrf1 induces antioxidant response element-mediated upregulation of UPS components in response to proteotoxic stress.

5-HT receptor-mediated modulation of granule cell inhibition after juvenile stress recovers after a second exposure to adult stress.

Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior.

Gating of hippocampal output by β-adrenergic receptor activation in the pilocarpine model of epilepsy.

Norepinephrine acting via β-adrenergic receptors (β-ARs) plays an important role in hippocampal plasticity including the subiculum which is the principal target of CA1 pyramidal cells and which controls information transfer from the hippocampus to other brain regions including the neighboring presubiculum and the entorhinal cortex (EC). Subicular pyramidal cells are classified as regular- (RS) and burst-spiking (BS) cells. Activation of β-ARs at CA1-subiculum synapses induces long-term potentiation (LTP) in burst- but not in RS cells (Wójtowicz et al.