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Background: Herpes simplex virus type 2 (HSV-2), the mostfrequent cause of genital ulcer disease (GUD), has been shown to play a moreimportant role than any other sexually transmitted infections (STIs) in drivingHIV prevalence in Africa. In turn, HIV-1 infection leads to more frequent HSV-2reactivations and shedding. The exact immune mechanisms involved in thisvirological negative immuno-synergy are unknown. In the present study we soughtto assess whether HIV co-infection would affects HSV-specific T cell immunity.Methods: Nineteen HSV peptides, derived from HSV-2glycoproteins gB and gD, were used to analyze the frequency and the magnitudeof HSV-2-specific IFN-γ-producing CD4+ and CD8+ T cellresponses in 30 HSV-2 seropositive patients and 17 HSV-2 seronegativeindividuals in a cohort of heterosexual Senegalese HIV-discordant couples,using ELISpot assay. HIV RNA viral load has been run for HIV infected subjects and CD4 count ran for all subjects using a flow cytometry method..Results: The magnitude and frequency HSV-2-specific Tcell responses was compared between 21 HSV-2 co-infected with HIV-1 and 9 HSV-2mono-infected individuals. A significantly higher magnitude of IFN-γ-producingT cell responses were observed in HSV-2 infected patients compared toseronegative individuals (median, 61 vs. 0 spots/106 PBMC, P= 0.001). Moreover, twenty-four (80%) out of 30 HSV-2 seropositive patientsshowed significant HSV-2-specific IFN-γ-producing T cell responses comparedwith only 6 (35%) out of 17 HSV-2 negative subjects (P < 0.001). TheHSV-2 mono-infected patients showed significantly higher magnitude ofHSV-2-specific T cell responses compared to HSV/HIV co-infected patients(median, 140 vs. 42 spots/106 PBMC, P = 0.024).Conclusions: Our finding suggest that co-infection with HIV-1 inHSV-2-infected patients might be associated with reduced HSV-2 cellular immuneresponses. However, the interaction between HIV and HSV-2 appears complex, andprecise longitudinal studies will be required to dissect their exact temporalrelationship.

BackgroundDown's syndrome (DS) is the most common genetic cause of mental retardation. Reduced number and aberrant architecture of dendritic spines are common features of DS neuropathology. However, the mechanisms involved in DS spine alterations are not known. In addition to a relevant role in synapse formation and maintenance, astrocytes can regulate spine dynamics by releasing soluble factors or by physical contact with neurons. We have previously shown impaired mitochondrial function in DS astrocytes leading to metabolic alterations in protein processing and secretion. In this study, we investigated whether deficits in astrocyte function contribute to DS spine pathology.Methodology/Principal FindingsUsing a human astrocyte/rat hippocampal neuron coculture, we found that DS astrocytes are directly involved in the development of spine malformations and reduced synaptic density. We also show that thrombospondin 1 (TSP-1), an astrocyte-secreted protein, possesses a potent modulatory effect on spine number and morphology, and that both DS brains and DS astrocytes exhibit marked deficits in TSP-1 protein expression. Depletion of TSP-1 from normal astrocytes resulted in dramatic changes in spine morphology, while restoration of TSP-1 levels prevented DS astrocyte-mediated spine and synaptic alterations. Astrocyte cultures derived from TSP-1 KO mice exhibited similar deficits to support spine formation and structure than DS astrocytes.Conclusions/SignificanceThese results indicate that human astrocytes promote spine and synapse formation, identify astrocyte dysfunction as a significant factor of spine and synaptic pathology in the DS brain, and provide a mechanistic rationale for the exploration of TSP-1-based therapies to treat spine and synaptic pathology in DS and other neurological conditions.

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although now behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps.