Thyroid hormone treated astrocytes induce maturation of cerebral cortical neurons through modulation of proteoglycan levels

Proper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within the sesignals, thyroid hormones (T3 and T4) play crucial role in several steps of brain morphogenesis including proliferation of progenitor cells, neuronal differentiation, maturation, migration, and synapse formation. the lack of thyroid hormones during childhood is associated with several impair neuronal connections, cognitive deficits, and mental disorders. Many of the thyroid hormones effects are mediated by astrocytes, although the mechanisms underlying these events are still unknown. in this work, we investigated the effect of 3,5,3'-triiodothyronine-treated (T3-treated) astrocytes on cerebral cortex neuronal differentiation. Culture of neural progenitors from embryonic cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in neuronal population, followed by enhancement of neuronal maturation, arborization and neurite outgrowth. in addition, real time PCR assays revealed an increase in the levels of the heparan sulfate proteoglycans, Glypican 1(GPC-1) and Syndecans 3 e 4 (SDC-3 e SDC-4), followed by a decrease in the levels of the chondroitin sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by chondroitinase AC or heparanase III completely abolished the effects of T3-treated astrocytes on neuronal morphogenesis. Our work provides evidence that astrocytes are key mediators of T3 actions on cerebral cortex neuronal development and identified potential molecules and pathways involved in neurite extension; which might eventually contribute to a better understanding of axonal regeneration, synapse formation, and neuronal circuitry recover.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Conselho Nacional para o Desenvolvimento Cientifico e TecnologicoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21949590 Rio de Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Bioquim Med, BR-21949590 Rio de Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, BR-21949590 Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilWeb of Scienc

Flavonoid Hesperidin Induces Synapse Formation and Improves Memory Performance through the Astrocytic TGF-β1

Synapse formation and function are critical events for the brain function and cognition. Astrocytes are active participants in the control of synapses during development and adulthood, but the mechanisms underlying astrocyte synaptogenic potential only began to be better understood recently. Currently, new drugs and molecules, including the flavonoids, have been studied as therapeutic alternatives for modulation of cognitive processes in physiological and pathological conditions. However, the cellular targets and mechanisms of actions of flavonoids remain poorly elucidated. In the present study, we investigated the effects of hesperidin on memory and its cellular and molecular targets in vivo and in vitro, by using a short-term protocol of treatment. The novel object recognition test (NOR) was used to evaluate memory performance of mice intraperitoneally treated with hesperidin 30 min before the training and again before the test phase. The direct effects of hesperidin on synapses and astrocytes were also investigated using in vitro approaches. Here, we described hesperidin as a new drug able to improve memory in healthy adult mice by two main mechanisms: directly, by inducing synapse formation and function between hippocampal and cortical neurons; and indirectly, by enhancing the synaptogenic ability of cortical astrocytes mainly due to increased secretion of transforming growth factor beta-1 (TGF-β1) by these cells. Our data reinforces the known neuroprotective effect of hesperidin and, by the first time, characterizes its synaptogenic action on the central nervous system (CNS), pointing astrocytes and TGF-β1 signaling as new cellular and molecular targets of hesperidin. Our work provides not only new data regarding flavonoid’s actions on the CNS but also shed light on possible new therapeutic alternative based on astrocyte biology

PEMF fails to enhance nerve regeneration after sciatic nerve crush lesion

Submitted by Martha Martínez Silveira ([email protected]) on 2015-04-15T12:32:40Z No. of bitstreams: 1 Baptista_et_al-2009-Journal_of_the_Peripheral_Nervous_System.pdf: 793307 bytes, checksum: 45e5d4b828f10d79b645abffdb63c872 (MD5)Approved for entry into archive by Martha Martínez Silveira ([email protected]) on 2015-04-15T12:59:17Z (GMT) No. of bitstreams: 1 Baptista_et_al-2009-Journal_of_the_Peripheral_Nervous_System.pdf: 793307 bytes, checksum: 45e5d4b828f10d79b645abffdb63c872 (MD5)Made available in DSpace on 2015-04-15T12:59:17Z (GMT). No. of bitstreams: 1 Baptista_et_al-2009-Journal_of_the_Peripheral_Nervous_System.pdf: 793307 bytes, checksum: 45e5d4b828f10d79b645abffdb63c872 (MD5) Previous issue date: 2009Universidade Federal da Bahia. Instituo de Ciências da Saúde. Departamento de Biomorfologia. Salvador, BA, Brasil / Universidade Federaldo Rio de Janeiro, Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Unidade de Microscopia Eletrônica. Salvador, BA, BrasilEscola Baiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Unidade de Microscopia Eletrônica. Salvador, BA, BrasilUniversidade Federaldo Rio de Janeiro, Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, BrasilEscola Baiana de Medicina e Saúde Pública. Salvador, BA, BrasilUniversidade Federaldo Rio de Janeiro, Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, BrasilEscola Baiana de Medicina e Saúde Pública. Salvador, BA, BrasilUniversidade Federaldo Rio de Janeiro, Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil / Escola Baiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Unidade de Microscopia Eletrônica. Salvador, BA, BrasilUniversidade Federaldo Rio de Janeiro, Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, BrasilThe use of electromagnetic fields has been reported to enhance peripheralnerve regeneration. This study aimed to identify the effects of a prolonged protocolof low-frequency pulsed electromagnetic field (PEMF) on peripheral nerve regeneration.Thirty-four male Swiss mice (Mus musculus) were divided into PEMF (n= 17) and control(n= 17) groups. All animals underwent a unilateral sciatic-crush lesion, and the PEMF groupwas exposed to a 72-Hz, 2-G electromagnetic field for 30 min, five days a week, for threeweeks. Functional analysis was carried out weekly. After three weeks, the animals wereeuthanized, and histological, morphometric, oxidative stress, and TGF-β1 analyses wereperformed. Functional analysis showed no differences between the groups. Histologicalappearance was similar between PEMF and control nerves. Morphometric assessmentshowed that the PEMF nerves trended toward decreased regeneration. The levels of freeradicals were more pronounced in PEMF nerves, but were not associated with an increasein the content of the TGF-β1/Smad signaling pathway. Prolonged PEMF regimen leads todelayed histological peripheral nerve regeneration and increased oxidative stress but noloss of function recover

Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling

Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood-brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19