The Acute Activation of the CB1 Receptor in the Hippocampus Decreases Neurotoxicity and Prevents Spatial Memory Impairment in Rats Lesioned with ß-Amyloid 25-35.

Given their anti-inflammatory properties, cannabinoids have been shown to be neuroprotective agents and to reduce excitotoxicity, through the activation of the Cannabinoid receptor type 1 (CB1r). These properties have led to CB1r being proposed as pharmacological targets for the treatment of various neurodegenerative diseases. Amyloid-ß 25-35 (Aß25-35) induces the expression of inducible nitric oxide synthase (iNOS) and increases nitric oxide (NO●) levels. It has been observed that increased NO● concentrations trigger biochemical pathways that contribute to neuronal death and cognitive damage. This study aimed to evaluate the neuroprotective effect of an acute activation of CB1r on spatial memory and its impact on iNOS protein expression, NO● levels, gliosis and the neurodegenerative process induced by the injection of Aß(25-35) into the CA1 subfield of the hippocampus. ACEA [1 µM/1 µL] and Aß(25-35) [100 µM/1 µL] and their respective vehicle groups were injected into the CA1 subfield of the hippocampus. The animals were tested for spatial learning and memory in the eight-arm radial maze, with the results revealing that the administration of ACEA plus Aß(25-35) improves learning and memory processes, in contrast with the Aß(25-35) group. Moreover, ACEA plus Aß(25-35) prevented both the increase in iNOS protein and NO● levels and the reactive gliosis induced by Aß(25-35). Importantly, neurodegeneration was significantly reduced by the administration of ACEA plus Aß(25-35) in the CA1 subfield of the hippocampus. The data obtained in the present research suggest that the acute early activation of CB1r is crucial for neuroprotection.

Neuroinflammation induced by the peptide amyloid-ß (25-35) increase the presence of galectin-3 in astrocytes and microglia and impairs spatial memory.

Galectins are animal lectins that bind to ß-galactosides, such as lactose and N-acetyllactosamine, contained in glycoproteins or glycolipids. Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are involved in pathologies associated with the inflammatory process, cell proliferation, adhesion, migration, and apoptosis. Recent evidence has shown that the administration of Amyloid-ß 25-35 (Aß25-35) into the hippocampus of rats increases the inflammatory response that is associated with memory impairment and neurodegeneration. Galectins could participate in the modulation of the neuroinflammation induced by the Aß25-35. The aim of this study was to evaluate the presence of Gal-1 and Gal-3 in the neuroinflammation induced by administration of Aß25-35 into the hippocampus and to examine spatial memory in the Morris water maze. After the administration of Aß25-35, animals were tested for learning and spatial memory in the Morris water maze. Behavioral performance showed that Aß25-35 didn't affect spatial learning but did impair memory, with animals taking longer to find the platform. On the day 32, hippocampus was examined for astrocytes (GFAP), microglia (Iba1), Gal-1 and Gal-3 via immunohistochemical analysis, and the cytokines IL-1ß, TNF-α, IFN-γ by ELISA. This study's results showed a significant increase in the expression of Gal-3 in the microglia and astrocytes, while Gal-1 didn't increase in the dorsal hippocampus. The expression of galectins is associated with increased cytokines in the hippocampal formation of Aß25-35 treated rats. These findings suggest that Gal-3 could participate in the inflammation induced by administration of Aß25-35 and could be involved in the neurodegeneration progress and memory impairment.

Neurogenesis and morphological-neural alterations closely related to amyloid ß-peptide (25-35)-induced memory impairment in male rats.

Memory impairment by the Amyloid-ß 25-35 (Aß25-35) peptide in animal models has provided an understanding of the causes behind the similar deterioration that occurs in Alzheimer's disease. However, it is uncertain if a decrease of dendritic spines and neurogenesis conduces to cognitive impairment by an impairment in the retrieval of stored memory. The aim of this study was to evaluate the consequences of impairment on spatial memory caused by the administration of the Aß25-35 peptide in the hippocampus, which is associated whit morphological changes and neurogenesis in the dentate gyrus (DG). The vehicle or Aß25-35 peptide (0.1µg/µL) were bilaterally administered in the CA1 subfield of the rat hippocampus. The animals were tested for spatial learning and memory in the Morris Water Maze. In the day's 11, 18 and 32 after administration of the Aß25-35 peptide were examined the morphological changes in the DG using a Golgi-Cox stain. In the day 32, the neurogenesis was evaluated by the immunoreactivity to 5-bromo-2'-deoxyuridine (BrdU; 100mg/kg, i.p.) that corresponding to cellular proliferation post damage, the neuronal specific nuclear protein (NeuN) and doublecortin (DCX). This study found a memory retrieval impairment occurring at day 17, a cognitive deficit which had increased significantly at day 31 after the administration of Aß25-35 peptide. These results are related to morphological changes in the granular cells of the DG, such as a shorter dendritic length and a decrease in the number of dendritic spines. In neurogenesis, the total number of cells positive to BrdU, NeuN and DCX in the hippocampal granule cell layer was found to have declined in animals treated with Aß25-35. The results suggest that the Aß25-35 peptide impairs memory retrieval by decreasing the number of dendritic spines and altering neurogenesis in the DG.

Alteration of the sialylation pattern and memory deficits by injection of Aß(25-35) into the hippocampus of rats.

Sialic acid in glycoconjugates participates in important cellular functions associated with normal development, growth, and communication. Therefore we evaluated the sialylation pattern and memory deficits caused by the injection of Aß((25-35)) into the hippocampus (Hp) of rats. The eight-arm maze spatial-learning and memory test indicated that the injection of Aß((25-35)) into subfield CA1 of the Hp impaired both learning and memory. The sialylation pattern was examined using sialic acid-specific lectins. Our results showed that Maackia amurensis agglutinin (MAA, specific for Neu5Acα2,3Gal) showed reactivity in the CA1 and dentate gyrus (DG) subfields of the Hp mainly in the group injected with vehicle, whereas Macrobrachium rosenbergii lectin (MRL, specific for Neu5,9,7Ac) and Sambucus nigra agglutinin (SNA, specific for Neu5Acα2,6Gal-GalNAc) had increased reactivity in the CA1 and DG subfields of the Hp in the Aß((25-35))-injected group. The staining pattern of the antibody specific for polysialic acid (a linear homopolymer of α-2,8-linked sialic acid) increased in the CA1 and DG subfields of the Hp of the Aß((25-35)) group compared to the control group. Our results suggest that injection of Aß((25-35)) causes impairment in spatial memory and alters the sialylation pattern in response to compensatory reorganization and-or sprouting of dendrites and axons of the surviving neurons.

Adolescent health risk behavior: when do pediatric psychologists break confidentiality?

OBJECTIVE: To determine the circumstances under which pediatric psychologists believe it is ethical to break confidentiality when presented with adolescent health risk behavior. METHOD: Members of the Society of Pediatric Psychology (N = 92) responded to a survey containing a vignette about an adolescent patient engaging in health-compromising behaviors. Participants rated the degree to which it is ethical to break confidentiality for health risk behaviors of varying frequency, intensity, and duration. RESULTS: Respondents generally find it ethical to break confidentiality when health risk behaviors are more intense, more frequent, and of longer duration. Respondents also find it more ethical to break confidentiality for female smoking than for male smoking. Similarly, they find it more ethical to break confidentiality for female sexual behavior than for male sexual behavior, but only as the frequency/duration increases. CONCLUSIONS: At a certain point, maintaining the adolescent's health is more important for pediatric psychologists than maintaining confidentiality.