Neuroscience
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Auditory brainstem networks facilitate sound source localization through binaural integration. A key component of this circuitry is the projection from the ventral cochlear nucleus (VCN) to the medial nucleus of the trapezoid body (MNTB), a relay nucleus that provides inhibition to the superior olivary complex. This strictly contralateral projection terminates in the large calyx of Held synapse. ⋯ We then determined the distribution of glial cells following early (P2) unilateral cochlear removal, which results in formation of ectopic projections from the intact VCN to ipsilateral MNTB. We found that following perturbation, astrocytic markers showed expression near the ectopic ipsilateral calyx. Taken together, the developmental expression patterns are consistent with a role for glial cells in the maturation of the calyx of Held and suggest that these cells may have a similar role in maturation of lesion-induced connections.
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Alterations in hippocampal neurogenesis affect spatial learning, though, the relative contributions of cell proliferation and cell survival on this process are poorly understood. The current study utilized mu opioid receptor (MOR-1) knockout (KO) mice on two background strains, C57BL/6 and 129S6, to assess cell survival as well as determine the impact on spatial learning using the Morris water maze. These experiments were designed to extend prior work showing that both C57BL/6 and 129S6 MOR-1 KO mice have an increased number of proliferating cells in the dentate gyrus (DG) when compared to wild-type (WT) mice. ⋯ These alterations collectively contribute to an increase in the granule cell number in the DG of C57BL/6 MOR-1 KO mice, while the total number of granule cells in 129S6 MOR-1 KO mice is unchanged. Thus, although C57BL/6 and 129S6 MOR-1 KO mice both exhibit increased cell proliferation in the DG, the impact of the MOR-1 mutation on cell survival differs between strains. Furthermore, the decrease in DG cell survival displayed by 129S6 MOR-1 KO mice is correlated with functional deficits in spatial learning, suggesting that MOR-1-dependent alterations in the survival of new neurons in the DG, and not MOR-1-dependent changes in proliferation of progenitor cells in the DG, is important for spatial learning.
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Accumulation of hypoxia-inducible transcription factors (HIFs) by prolyl-4-hydroxylase inhibitors (PHI) has been suggested to induce neuroprotection in the ischemic rodent brain. We aimed to investigate in vivo effects of a novel PHI on HIF-regulated neurotrophic and pro-apoptotic factors in the developing normoxic and hypoxic mouse brain. ⋯ PHI treatment modulates neurotrophic factors known to be crucially involved in hypoxia-induced cerebral adaptive mechanisms as well as early brain maturation. Pre-treatment with FG-4497 seems to protect the developing brain from hypoxia-induced apoptosis. Present observations provide basic information for further evaluation of neuroprotective properties of PHI treatment in hypoxic injury of the developing brain. However, potential effects on maturational processes need special attention in experimental research targeting HIF-dependent neuroprotective interventions during the very early stage of brain development.
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Alzheimer's disease (AD) is the most common and devastating neurodegenerative disease. The etiology of AD has yet to be fully understood, and common treatments remain largely non-efficacious. The amyloid hypothesis posits that extracellular amyloid-β (Aβ) deposits are the fundamental etiological factor of the disease. ⋯ Chronic exposure to (PhSe)2 attenuated oxidative stress induced by Aβ1-42, with concomitant recovery of associative learning memory in C. elegans. Additionally, (PhSe)2 decreased Aβ1-42 transgene expression, suppressed Aβ1-42 peptide, and downregulated hsp-16.2 by reducing the need for this chaperone under Aβ1-42-induced toxicity. These observations suggest that (PhSe)2 plays an important role in protecting against oxidative stress-induced toxicity, thus representing a promising pharmaceutical modality that attenuates Aβ1-42 expression.
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The recent decade testified a tremendous increase in our knowledge on how cell-type-specific microcircuits process sensory information in the neocortex and on how such circuitry reacts to manipulations of the sensory environment. Experience-dependent plasticity has now been investigated with techniques endowed with cell resolution during both postnatal development and in adult animals. ⋯ I will also discuss on which scientific problems the debate and controversies are more pronounced. New technologies that allow to perturbate cell-type-specific subcircuits will certainly shine new light in the years to come at least on some of the still open questions.