Neuroscience
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Stress evokes age-dependent effects on pain sensitivity and commonly occurs during adolescence. However, the mechanisms linking adolescent stress and pain remain poorly understood, in part due to a lack of information regarding how stress hormones modulate the function of nociceptive circuits in the adolescent CNS. Here we investigate the short- and long-term effects of corticosterone (CORT) on the excitability of GABAergic and presumed glutamatergic neurons of the spinal superficial dorsal horn (SDH) in Gad1-GFP mice at postnatal days (P)21-P34. ⋯ Meanwhile, the acute bath application of CORT significantly decreased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs), as well as the frequency of miniature inhibitory postsynaptic currents (mIPSCs), in both cell types leading to a net reduction in the balance of spontaneous excitation vs. inhibition (E:I ratio). This CORT-induced reduction in the E:I ratio was not prevented by selective antagonists of either GR (mifepristone) or MR (eplerenone), although eplerenone blocked the effect on mEPSC amplitude. Collectively, these data suggest that corticosterone modulates synaptic function within the adolescent SDH which could influence the overall excitability and output of the spinal nociceptive network.
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The major immune cells of the central nervous systems (CNS) are microglia and astrocytes, subsets of the glial cell population. The crosstalk between glia via soluble signaling molecules plays an indispensable role for neuropathologies, brain development as well as homeostasis. However, the investigation of the microglia-astrocyte crosstalk has been hampered due to the lack of suitable glial isolation methods. ⋯ Finally, co-culturing microglia and astrocytes confirmed the prior results by demonstrating a significant TNF release by WT microglia co-cultured with TLR2-KO astrocytes. Our findings suggest a molecular TLR2/1-dependent conversation between highly pure activated microglia and astrocytes via signaling molecules. Furthermore, we demonstrate the first crosstalk experiments using ∼100% pure microglia and astrocyte mono-/co-cultures derived from mice with different genotypes highlighting the urgent need of efficient glial isolation protocols, which particularly holds true for astrocytes.
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Africa is home to a longstanding tradition of scientific enquiry dating back to the Pharaohs. In the last century, Africa's universities were instrumental in nation building and in training expertise in many fields of scientific endeavor, including neuroscience. In 1988 IBRO, committed to neuroscience development in Africa, organized a workshop at the University of Nairobi to bring African neuroscientists together to discuss advancement of the discipline on the continent. ⋯ Since then, IBRO has continued its support for African neuroscience through several initiatives including organization of a series of high-level schools in Africa that have kept the continent's educators and researchers abreast of the latest advances and technological tools in the discipline. The rapid development of new neuroscience methodologies for the treatment and enhancement of brain function, including brain stimulation, pharmaceutical treatment of psychiatric disorders, and stem cell transplants to treat neurodegenerative diseases create research environments in which Africa's rich genetic diversity and its medicinal plant resources can play an important role. The continued support of IBRO to African neuroscience over the past 35 years has contributed effectively to laying the groundwork for a new sense of community that Africa's educators need to develop further through cooperation in defining curricula and joint research projects.
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Cell quiescence is an essential mechanism that allows cells to temporarily halt proliferation while preserving the potential to resume it at a later time. The molecular mechanisms underlying cell quiescence are complex and involve the regulation of various signaling pathways, transcription factors and epigenetic modifications. The importance of unveiling the mechanisms regulating the quiescent state is undeniable, as its long-term maintenance is key to sustain tissue homeostasis throughout life. ⋯ Differently from other non-proliferative states, quiescence is a reversible and tightly regulated condition that can re-activate to support the formation of new neurons throughout adult lifespan. Decoding its regulatory mechanisms in homeostasis and unveiling how it is modulated in the context of the aged brain or during tumorigenesis, could bring us closer to the development of new potential strategies to intervene in adult neurogenesis with therapeutic purposes. Starting with a general conceptualization of the quiescent state in different stem cell niches, we here review what we have learned about NSC quiescence in the SEZ, encompassing the experimental strategies used for its study, to end up discussing the modulation of quiescence in the context of a physiology or pathological NSC dysregulation.