1,721,031 research outputs found
Free radical scavenging and inhibition of nitric oxide synthase potentiates the neurotrophic effects of brain-derived neurotrophic factor on axotomized retinal ganglion cells in vivo
No full textBrain-derived neurotrophic factor (BDNF) partially promotes the survival of axotomized retinal ganglion cells (RGCs). In analogy with in vitro experiments (Koh et al., 1995; Samdami et al., 1996), we tested whether neuroprotection by BDNF is limited by adverse effects as a consequence of excessive free radical formation. First, we investigated whether BDNF and the free radical scavenger N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN) cooperate in protecting RGCs from axotomy-induced death. Although systemic S-PBN treatment alone did not influence RGC survival after axotomy, it potentiated the neuroprotective effects of BDNF significantly. Single BDNF treatment rescued 27% of the RGCs, which otherwise would have died 14 d after optic nerve transection, whereas a combined treatment of BDNF and S-PBN improved this rescue rate up to 68%. We then investigated whether the adverse effects of BDNF could be ascribed to activation of nitric oxide synthase (NOS). We found colocalization of NOS and the BDNF receptor TrkB in the retina. NADPH-diaphorase reactivity, a reliable marker for NOS in the rat retina, increased after chronic BDNF treatment in vivo. Systemic application of the NOS-inhibitor N-omega-nitro-L-arginine-methylester (L-NAME) potentiated the neuroprotective action of BDNF (55% rescue rate). We conclude that activation of NOS is a pathological consequence of BDNF application, which reduces its neuroprotective potential. The observation that this adverse effect can be antagonized by systemic application of free radical scavengers could be of relevance for clinical applications of neurotrophins in human neurodegenerative diseases
The distribution of Brain Derived Neurotrophic factor and its receptor trkB in parvalbumin containing neurons of the rat visual cortex
No full textMONOCULAR DEPRIVATION EFFECTS IN THE RAT VISUAL-CORTEX AND LATERAL GENICULATE-NUCLEUS ARE PREVENTED BY NERVE GROWTH-FACTOR (NGF) .2. LATERAL GENICULATE-NUCLEUS
No full textIn the preceding paper (Berardi et al. Proc. R. Soc. Lond. B 251, 17 (1993)), it has been shown that nerve growth factor (NGF) prevents the functional and anatomical alterations induced by monocular deprivation (MD) at the level of the visual cortex. Here we report that an exogenous supply of NGF prevents the shrinkage of neurons in the deprived laminae of lateral geniculate nucleus (LGN). The soma size distribution for the deprived ipsilateral laminae Of MD rats is shifted towards smaller sizes (mean percentage of shrinkage with respect to the ipsilateral undeprived lamina = 21%, s.d. = 2%). As in other mammals, MD affects LGN relay neurons and spares LGN neurons projecting to the monocular portion of primary visual cortex. In NGF-treated animals we found that the soma size distributions for the deprived and undeprived ipsilateral laminae extensively overlap. The, results of the two papers show that an exogenous supply of NGF prevents MD effects at both levels, visual cortex and LGN, and suggest a role for NGF in the plasticity of the geniculo-cortical pathway
Apoptosis in the developing visual system
No full textProgramed cellular death is a widespread phenomenon during development of the nervous system. Two classes of molecules are particularly important in the context of apoptosis control in the nervous system: intracellular effecters homologous to the Caenorhabditis elegans Ced-3, -4, and -9 proteins, which in mammals correspond to the proteases of the caspase family, Apaf-1, and the members of the Bcl-2 protein family, and neurotrophic factors. Retinal ganglion cells lend a convenient model system with which to investigate apoptosis in central neurons during development as well as after injury. In this review, we discuss the role of these molecules in the control of programed cellular death in the retinotectal system. Transgenic animal models and expression studies have shown that caspases, Bcl-2, Bax, and possibly Bcl-X are necessary players for the control of programed cellular death in retinal ganglion cells. Bax and caspase 3 expression in retinal ganglion cells is upregulated after injury, and inhibition of Bax or caspase 3 increases the survival of injured retinal ganglion cells. Neurotrophins can support the survival of injured retinal ganglion cells, but this effect is transient. The physiological role of neurotrophins in the development of the retinocollicular system seems more related to the topographic refinement of retinocollicular projections, a process that is mediated, at least partially, by selective elimination of retinal ganglion cells making inappropriate topographic projections
Effetto Della Restrizione Calorica Sulle Modificazioni Epatiche Legate Ai Processi Di Invecchiamento Nel Modello Animale Killifish Turchese (Nothobranchius Furzeri, Jubb 1971).
No full textADVANCED GLYCATION END PRODUCTS AND THEIR INVOLVEMENT IN TURQUOISE KILLIFISH (NOTHOBRANCHIUS FURZERI, JUBB 1971) LIVER PATHOLOGIES.
No full textExcess target-derived brain-derived neurotrophic factor preserves the transient uncrossed retinal projection to the superior colliculus
No full textDuring early postnatal development, a widespread ipsilateral projection to the superior colliculus is secondarily restricted to a small topographically defined region by elimination of ipsilaterally projecting retinal ganglion cells. Brain-derived neurotrophic factor (BDNF) has been proposed as the target-derived neurotrophic factor for retinal ganglion cells in several studies. Here we investigated the long-term effects of excess BDNF in the retinal ganglion cell target on naturally occurring retinal ganglion cell (RGC) elimination and on the restriction of the ipsilateral projection. To this end, sustained overexpression of BDNF was achieved in the postnatal superior colliculus using an adenoviral vector. While the total number of retinal ganglion cells in the adenovirus-BDNF treated animals was unchanged, a much higher proportion of RGCs retained a projection to the ipsilateral superior colliculus. We conclude that an excess of target-derived BDNF does not reduce the net amount of naturally occurring cell death in the retino-collicular system, but prevents the negative selection of retinal ganglion cells making inappropriate topographic connections
The sources of sex differences in aging in annual fishes
Full text linkIntersexual differences in life span (age at death) and aging (increase in mortality risk associated with functional deterioration) are widespread among animals, from nematodes to humans. Males often live shorter than females, but there is substantial unexplained variation among species and populations. Despite extensive research, it is poorly understood how life span differences between the sexes are modulated by an interplay among genetic, environmental and social factors. The goal of our study was to test how sex differences in life span and ageing are modulated by social and environmental factors, and by intrinsic differences between males and females. To disentangle the complex basis of sex differences in life span and aging, we combined comparative data from sex ratios in 367 natural populations of four species of African annual killifish with experimental results on sex differences in life span and aging from eight laboratory populations tested in treatments that varied social and environmental conditions. In the wild, females consistently outlived males. In captivity, sex-specific mortality depended on social conditions. In social-housed experimental groups, male-biased mortality persisted in two aggressive species, but ceased in two placid species. When social and physical contacts were prevented by housing all fish individually, male-biased mortality ceased in all four species. This outcome held across benign and challenging environmental conditions. Fitting demographic survival models revealed that increased baseline mortality was primarily responsible for a shorter male life span in social-housing conditions. The timing and rate of aging were not different between the sexes. No marker of functional aging we recorded in our study (lipofuscin accumulation, proliferative changes in kidney and liver) differed between males and females, despite their previously confirmed association with functional aging in Nothobranchius killifish. We show that sex differences in life span and aging in killifish are driven by a combination of social and environmental conditions, rather than differential functional aging. They are primarily linked to sexual selection but precipitated through multiple processes (predation, social interference). This demonstrates how sex-specific mortality varies among species even within an ecologically and evolutionary discrete lineage and explains how external factors mediate this difference.Intersexual differences in life span (age at death) and aging (increase in mortality risk associated with functional deterioration) are widespread among animals, from nematodes to humans. Males often live shorter than females, but there is substantial unexplained variation among species and populations. Despite extensive research, it is poorly understood how life span differences between the sexes are modulated by an interplay among genetic, environmental and social factors. The goal of our study was to test how sex differences in life span and ageing are modulated by social and environmental factors, and by intrinsic differences between males and females. To disentangle the complex basis of sex differences in life span and aging, we combined comparative data from sex ratios in 367 natural populations of four species of African annual killifish with experimental results on sex differences in life span and aging from eight laboratory populations tested in treatments that varied social a..
Antibodies to nerve growth factor (NGF) prolong the sensitive period for monocular deprivation in the rat
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