Neuroscience
-
Tau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. ⋯ Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tau-induced activation of glycogen synthase kinase-3β (GSK-3β) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-3β signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.
-
Environmental enrichment (EE) is a condition characterized by its complexity regarding social contact, exposure to novelty, tactile stimuli and voluntary exercise, also is considered as a eustress model. The impact of EE on brain physiology and behavioral outcomes may be at least partly underpinned by mechanisms involving the modulation of the brain-derived neurotrophic factor (BDNF), but the connection between specific Bdnf exon expression and their epigenetic regulation remain poorly understood. This study aimed to dissect the transcriptional and epigenetic regulatory effect of 54-day exposure to EE on BDNF by analysing individual BDNF exons mRNA expression and the DNA methylation profile of a key transcriptional regulator of the Bdnf gene, exon IV, in the prefrontal cortex (PFC) of C57BL/6 male mice (sample size = 33). ⋯ However, no changes were observed in EE mice. The findings may suggest an EE-induced epigenetic control of BDNF exon expression via a mechanism involving exon IV methylation. The findings of this study contribute to the current literature by dissecting the Bdnf gene topology in the PFC where transcriptional and epigenetic regulatory effect of EE takes place.
-
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.
-
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.
-
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.