On the participation of hippocampal p38 mitogen-activated protein kinase in extinction and reacquisition of inhibitory avoidance memory.

Inhibitory avoidance (IA) learning relies on the formation of an association between stepping down from a platform present in a certain context (conditioned stimulus; CS) with an aversive unconditioned stimulus (US; i.e. a footshock). A single CS-US pairing establishes a robust long-term memory expressed as an increase in step-down latency at testing. However, repeated retrieval of the avoidance response in the absence of the US induces extinction of IA memory. That is, recurring presentation of the CS alone results in a new learning indicating that the CS no longer predicts the US. Although the signaling pathways involved in the consolidation of IA and other fear-motivated memories have been profusely studied, little is known about the molecular requirements of fear memory extinction. Here we report that, as happens with its consolidation, extinction of IA long-term memory requires activity of the p38 subfamily of mitogen-activated protein kinases (MAPK) in the CA1 region of the dorsal hippocampus. Moreover, we found that inhibition of hippocampal p38MAPK blocked memory reacquisition after extinction without affecting either the increase in IA memory retention induced by a second training session or animal's locomotor/exploratory activity and anxiety state.

[Cryptococcus meningitis: clinical course, development and histopathologic aspects depending on the predisposing factors]. / Meningite criptocócica: aspectos clínicos, evolutivos e histopatológicos segundo a condição predisponente.

Seventeen consecutive cases of cryptococcal meningitis diagnosed at Hospital das Clínicas of Ribeirão Preto Medical School (São Paulo State Brazil) between 1969 and 1985 were reviewed. For analysis the patients were separated in 3 groups: I. three patients without immunodeficiency; II. six patients with associated disease: cancer (3), diabetes (2) and alcoholism (1); III. Eight renal transplant recipients that developed cryptococcosis after 18 to 67 months of immunosupression with steroids and azathioprine. The median interval between onset of symptoms and diagnosis of infection was greater in Group II (53 days) than in Groups I (25 days) or III (28 days). Neck stiffness, cranial nerve involvement and papilledema were more frequent in Group I than in Group II or III, but fever and focal neurological signs were observed only in patients of two last groups. Cerebrospinal fluid examination showed a mild lymphocytic pleocytosis in most patients, but transplant cases had polymorphonuclear cells more frequently. Late mortality was higher in patients with underlying disease and the prognosis was better for transplant patients that received effective antifungal therapy. Besides cryptococci, autopsy findings in 8 cases revealed granuloma formation in tissues, except in patients of Group II (2 cases). The differences between the groups suggest that clinical characteristics, evolution and postmortem findings of the cryptococcal meningitis are changed according to type of immunodeficiency presented by the patient.