Current and emerging molecular targets in glioma.

Gliomas are the most common and lethal neurological cancers. Despite research efforts, the prognosis for patients with malignant gliomas remains poor. Advances in the understanding of cellular and molecular alterations in gliomas have led to the emergence of experimental molecularly targeted therapies.

Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels.

The non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine has been shown to produce cognitive deficits. However, the effects of ketamine on the consolidation phase of memory remain poorly characterized. Here we show that systemic administration of ketamine immediately after training dose-dependently impairs long-term retention of memory for a novel object recognition (NOR) task in rats.

A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic Properties and Impairs Recognition But Not Aversive Memory in Mice.

Plants of the genus Valeriana (Valerianaceae) are used in traditional medicine as a mild sedative, antispasmodic and tranquilizer in many countries. This study was undertaken to explore the neurobehavioral effects of systemic administration of a valepotriate extract fraction of known quantitative composition of Valeriana glechomifolia (endemic of southern Brazil) in mice. Adult animals were treated with a single intraperitoneal injection of valepotriate fraction (VF) in the concentrations of 1, 3 or 10 mg kg(-1), or with vehicle in the pre-training period before each behavioral test.

Retrieval mediated by hippocampal extracellular signal-regulated kinase/mitogen-activated protein kinase is required for memory strengthening.

Established memories can be strengthened by additional learning and rehearsal. However, the brain processes enabling memories to be updated by further information is unclear. We found that blockade of retrieval of a stabilized memory by inhibition of the extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in the hippocampus prevented memory enhancement induced by an additional learning trial in rats.

Alterations in oxidative markers in the cerebellum and peripheral organs in MPS I mice.

Mucopolysaccharidosis type I is a lysosomal storage disease with alterations in several organs. Little is known about the pathways that lead to the pathology. Evidences point oxidative stress on lysosomal storage diseases and mucopolysaccharidosis type I.

A synaptic reinforcement-based model for transient amnesia following disruptions of memory consolidation and reconsolidation.

The observation of memory recovery following post-training amnestic interventions has historically caused controversy over the meaning of this finding, leading some authors to question the paradigm of a consolidation period for memories. Similarly, recent demonstrations of transient amnesia caused by interventions following memory reactivation have been used to question the existence of a retrieval-driven reconsolidation process. The present work aims to approach the phenomenon of transient amnesia following disruptions of consolidation and reconsolidation, discussing how memory recovery might be explained within a framework of systems consolidation, persistent synaptic reinforcement, and multiple memory traces.

Transient disruption of fear-related memory by post-retrieval inactivation of gastrin-releasing peptide or N-methyl-D-aspartate receptors in the hippocampus.

Molecular accounts of memory consolidation suggest that new learning generates persistent synaptic modifications through activation of an extensive set of neuronal receptors and intracellular signal transduction pathways, accompanied by RNA and protein synthesis. This traditional cellular consolidation theory has been challenged by evidence that reactivation of a previously consolidated memory might render this memory again susceptible to disruption by amnesic treatments, a process generally referred to as reconsolidation. Current evidence indicates that reconsolidation can be disrupted by administration of a variety of pharmacological agents after memory reactivation.

The gastrin-releasing peptide receptor as a therapeutic target in central nervous system disorders.

Gastrin-releasing peptide (GRP) is a mammalian counterpart of the amphibian peptide bombesin (BB) that stimulates cell proliferation, acts as a growth factor in the pathogenesis of many types of cancer, and regulates several aspects of neuroendocrine function. BB and GRP act by binding to the GRP-preferring type of BB receptor (GRPR, also known as BB2 receptor), a member of the superfamily of G-protein coupled membrane receptors. This review summarizes recent evidence from animal and human studies indicating that abnormalities in GRPR function in the brain might play a role in the pathogenesis of neurological and psychiatric disorders, and suggesting that BB, GRP, and GRPR antagonists might display therapeutic actions in central nervous system diseases.

A gastrin-releasing peptide receptor antagonist blocks D-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats.

The gastrin-releasing peptide receptor (GRPR) has emerged as a novel molecular target in neurological and psychiatric disorders, and previous animal studies suggest that GRPR antagonists might display cognitive-enhancing and antipsychotic properties. Hyperlocomotion produced by administration of D-amphetamine (D-AMPH) to rats has been put forward as a model of the manic phase of bipolar disorder (BD). In the present study, we examined the effects of a single systemic administration of the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095) on hyperlocomotion induced by a single systemic injection of D-AMPH in male rats.

Basic fibroblast growth factor prevents the memory impairment induced by gastrin-releasing peptide receptor antagonism in area CA1 of the rat hippocampus.

Increasing evidence indicates that the gastrin-releasing peptide receptor (GRPR) is implicated in regulating synaptic plasticity and memory formation in the hippocampus and other brain areas. However, the molecular mechanisms underlying the memory-impairing effects of GRPR antagonism have remained unclear. Here we report that basic fibroblast growth factor (bFGF/FGF-2) rescues the memory impairment induced by GRPR antagonism in the rat dorsal hippocampus.

Targeting the gastrin-releasing peptide receptor pathway to treat cognitive dysfunctionassociated with Alzheimer's Disease.

Increasing evidence indicates that bombesin (BB)-like peptides (BLPs), such as the gastrin-releasing peptide (GRP) and its receptor (GRPR), might play a role in neurological and psychiatric disorders. The present study reviews findings from animal and human studies suggesting that the GRPR should be considered a target for the treatment of cognitive dysfunction in patients with Alzheimer's disease (AD). Abnormalities in GRPR-triggered signaling have been described in both fibroblasts from patients with AD, and in transgenic mouse models of AD.

Aversive learning under different training conditions: effects of NMDA receptor blockade in area CA1 of the hippocampus.

Adult male Wistar rats were given either a single training trial or one training trial per day during 3 days followed by a retention test trial in an inhibitory avoidance (IA) task. In animals given a single training trial, pretraining, but not pretest bilateral infusion of the NMDA glutamate receptor antagonist d,l-2-amino-5-phosphonopentanoic acid (AP5) (5.0 microg) into the CA1 hippocampal area blocked IA retention.

A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory.

Although the gastrin-releasing peptide receptor has been implicated in memory consolidation, previous studies have not examined whether it is involved in extinction. Here we show that gastrin-releasing peptide receptor blockade in the hippocampus disrupts extinction of aversive memory. Male rats were trained in inhibitory avoidance conditioning and then returned repeatedly to the training context without shock on a daily basis for 3 days.

Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus.

Although the gastrin-releasing peptide-preferring bombesin receptor (GRPR) has been implicated in memory formation, the underlying molecular events are poorly understood. In the present study, we examined interactions between the GRPR and cellular signaling pathways in influencing memory consolidation in the hippocampus. Male Wistar rats received bilateral infusions of bombesin (BB) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training.

Opposite effects of low and high doses of the gastrin-releasing peptide receptor antagonist RC-3095 on memory consolidation in the hippocampus: possible involvement of the GABAergic system.

Although the gastrin-releasing peptide receptor (GRPR) has recently emerged as a system importantly involved in regulating memory formation, the role of hippocampal GRPRs in memory remains controversial. The present study examined the effects of GRPR antagonism on memory consolidation in area CA1 of the hippocampus. Male Wistar rats received bilateral infusions of the GRPR antagonist [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6-14) (RC-3095; 1, 3, or 10 microg/side) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training.

Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders.

The mammalian bombesin (BB)-like peptide gastrin-releasing peptide (GRP) stimulates cell proliferation, displays a range of neuroendocrine activities, and acts as a growth factor in the pathogenesis of several types of human cancer. Several lines of evidence have indicated that GRP and its receptor (GRPR) might also be involved in the neurochemical alterations associated with psychiatric and neurological disorders. GRP and GRPR are distributed throughout the mammalian central nervous system (CNS).

Long-term memory for aversive training is impaired in Idua(-/-) mice, a genetic model of mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease that leads to neurodegeneration and neurological deficits, among other pathological and clinical consequences. The aim of the present study was to evaluate neurobehavioral parameters in a genetic mouse model of mucopolysaccharidosis type I (MPS I). During exploration of an open field, adult MPS I (Idua(-/-)) mice showed normal locomotion and anxiety but reduced number of rearings.

NMDA receptors mediate consolidation of contextual memory in the hippocampus after context preexposure.

Male Wistar rats received bilateral infusions of vehicle (VEH) or aminophosphonopentanoic acid (AP5), an N-metil-D-aspartate (NMDA) receptor antagonist, into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intrahippocampal infusion of AP5 blocked 24 h IA retention. In the second experiment, animals were preexposed to the IA training context 24 h prior to training and received an infusion of either VEH or AP5 immediately after the preexposure trial and a second infusion of VEH or AP5 immediately after IA training.

Bombesin/gastrin-releasing peptide receptors in the basolateral amygdala regulate memory consolidation.

Several receptor and intracellular signalling systems in the basolateral amygdala (BLA) regulate memory formation. In the present study, we show that bombesin/gastrin-releasing peptide (GRP) receptors in the BLA are involved in the consolidation of affectively motivated memory. Adult male rats were trained in a single-trial step-down inhibitory avoidance task and tested for retention 24 h later.

RC-3095, a bombesin/gastrin-releasing peptide receptor antagonist, impairs aversive but not recognition memory in rats.

Bombesin and its mammalian equivalent, gastrin-releasing peptide (GRP), stimulate cell proliferation and are involved in the pathogenesis of several types of human cancer. Bombesin-like peptides also display neuroendocrine activities and regulate neural function. In the present study, we evaluated the effects of the bombesin/GRP receptor antagonist (D-Tpi(6), Leu(13) psi[CH(2)NH]-Leu(14)) bombesin-(6-14) (RC-3095), experimental antitumor drug, on memory in rats.