Neuroscience
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Schizophrenia (SZ) is a neurodevelopmental-associated disorder strongly related to environmental factors, such as hypoxia. Because there is no cure for SZ or any pharmacological approach that could revert hypoxia-induced cellular damages, we evaluated whether modulators of sirtuins could abrogate hypoxia-induced mitochondrial deregulation as a neuroprotective strategy. Firstly, astrocytes from control (Wistar) and Spontaneously Hypertensive Rats (SHR), a model of both SZ and neonatal hypoxia, were submitted to chemical hypoxia. ⋯ Our data indicate that sirtuins modulation reduces cell death increasing the acetylation of histone 3. This outcome is related to the rescue of loss of mitochondrial membrane potential, changes in mitochondrial calcium buffering capacity, decreased O2-rad levels and increased expression of metabolic regulators (Nrf-1 and Nfe2l2) and mitochondrial content. Such findings are relevant not only for hypoxia-associated conditions, named pre-eclampsia but also for SZ since prenatal hypoxia is a relevant environmental factor related to this burdensome neuropsychiatric disorder.
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Dopamine (DA) is a critical neuromodulator involved in various brain functions. To understand how DA regulates neural circuits and behaviors in the physiological and pathological conditions, it is essential to have tools that enable the direct detection of DA dynamics in vivo. Recently, genetically encoded DA sensors based on G protein-coupled receptors revolutionized this field, as it allows us to track in vivo DA dynamic with unprecedented spatial-temporal resolution, high molecular specificity, and sub-second kinetics. ⋯ Then we focus on the development of genetically encoded DA sensors and feature its significance to understanding dopaminergic neuromodulation across diverse behaviors and species. Finally, we present our perspectives about the future direction of the next-generation DA sensors and extend their potential applications. Overall, this review offers a comprehensive perspective on the past, present, and future of DA detection tools, with important implications for the study of DA functions in health and disease.
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Allergic asthma is a common chronic inflammatory condition associated with psychiatric comorbidities. Notably depression, correlated with adverse outcomes in asthmatic patients. Peripheral inflammation's role in depression has been shown previously. ⋯ Moreover, mPFC and vHipp activity were altered in asthmatic animals. Allergen disrupted the strength and direction of functional connectivity in the mPFC-vHipp circuit so that, unlike normal conditions, mPFC causes and modulates vHipp activity. Our results provide new insight into the underlying mechanism of allergic inflammation-induced psychiatric disorders, aiming to develop new interventions and therapeutic approaches for improving asthma complications.
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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.
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This chapter presents a brief overview of attachment theory and discusses the importance of the neonatal period in shaping an individual's physiological and behavioural responses to stress later in life, with a focus on the role of the parent-infant relationship, particularly in rodents. In rodents, the role of maternal behaviours goes far beyond nutrition, thermoregulation and excretion, acting as hidden regulators of the pup's physiology and development. In this review, we will discuss the inhibitory role of specific maternal behaviours on the ACTH and corticosterone (CORT) stress response. ⋯ These findings create an opportunity to explore the neurobiological underpinnings of vulnerability and resilience to stress-related disorders. The chapter also provides a brief historical overview and highlights the relevance of attachment theory, and how DEP helps to understand the effects of childhood parental loss as a risk factor for depression, schizophrenia, and PTSD in both childhood and adulthood. Furthermore, we present the concept of environmental enrichment (EE), its effects on stress responses and related behavioural changes and its benefits for rats previously subjected to DEP, along with the clinical implications of DEP and EE.