No abstract

In the past decades, the cellular and molecular mechanisms underlying memory consolidation, reconsolidation, and extinction have been well characterized. However, the neurobiological underpinnings of forgetting processes remain to be elucidated. Here we used behavioral, pharmacological and electrophysiological approaches to explore mechanisms controlling forgetting. We found that post-acquisition chronic inhibition of the N-methyl-D-aspartate receptor (NMDAR), L-type voltage-dependent Ca2+ channel (LVDCC), and protein phosphatase calcineurin (CaN), maintains long-term object location memory that otherwise would have been forgotten. We further show that NMDAR activation is necessary to induce forgetting of object recognition memory. Studying the role of NMDAR activation in the decay of the early phase of long-term potentiation (E-LTP) in the hippocampus, we found that ifenprodil infused 30 min after LTP induction in vivo blocks the decay of CA1-evoked postsynaptic plasticity, suggesting that GluN2B-containing NMDARs activation are critical to promote LTP decay. Taken together, these findings indicate that a well-regulated forgetting process, initiated by Ca2+ influx through LVDCCs and GluN2B-NMDARs followed by CaN activation, controls the maintenance of hippocampal LTP and long-term memories over time.

This study showed that the biological properties of the folk medicinal plants Lycopodium clavatum and Lycopodium thyoides include AChE inhibitory activity and antioxidant effects, two possible mechanisms of action in Alzheimer's related processes.

Although inflammation may be a physiological defense process, imbalanced neuroinflammation has been associated with the pathophysiology of brain disorders, including major depression and schizophrenia. Activated glia releases a variety of pro-inflammatory cytokines that contribute to neuronal dysfunction. Elevated levels of S100B, a glia derived protein, have been observed in the serum and CSF of schizophrenic patients suggesting a glial role in the disease. We evaluated whether S100B secretion (in C6 glioma cells and hippocampal slices in Wistar rats) could be directly modulated by the main inflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-8) altered in schizophrenia, as well as the possible involvement of mitogen-activated protein kinase (MAPK) pathways in these responses. We also investigated the effects of typical and atypical antipsychotic drugs on glial cytokine-induced S100B release. Our results suggest that S100B secretion is increased by pro-inflammatory cytokines via MAPK and that oxidative stress may be a component of this modulation. These results reinforce the idea that the S100B protein is involved in the inflammatory response observed in many brain diseases, including schizophrenia. Moreover the antipsychotics, haloperidol and risperidone, were able to inhibit the secretion of S100B following IL-6 stimulation in C6 glioma cells.

Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA) animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP) of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND) 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders.