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Plant proteins are garnering interest due to the growing demand for plant-based products, but their functionality in gel-based foods remains limited. Ultrasound (US) technology may improve the technological properties of proteins. Thus, the effect of US treatment time (0–15 min) on the structure and gelling properties of pea, lupin, and rice proteins was evaluated. The results showed that the whiteness (~60%) of all freeze-dried proteins remained unchanged (p > 0.05), regardless of the US time. However, FT-IR analysis revealed progressive reductions in α-helix and β-sheet for pea and lupin proteins (~50%) with US time, indicating partial unfolding. In addition, microstructure analysis showed an ~80% reduction in aggregate size for these proteins, while rice protein exhibited minimal changes. Conversely, weak gels were formed with pea and lupin proteins treated after 5 and 10 min of US, respectively, whereas rice protein did not form gels. Furthermore, US treatment time significantly increased (p < 0.05) the mechanical moduli, resulting in more structured gels after longer treatment times (tan δ ~0.3 at 15 min of US). These findings suggest that US treatment enhances the gelling properties of pea and lupin proteins, making them more suitable for plant-based food applications such as yogurt or desserts.

A major goal of neuroscience is understanding how neurons arrange themselves into neural networks that result in behavior. Most theoretical and experimental efforts have focused on a top-down approach which seeks to identify neuronal correlates of behaviors. This has been accomplished by effectively mapping specific behaviors to distinct neural patterns, or by creating computational models that produce a desired behavioral outcome. Nonetheless, these approaches have only implicitly considered the fact that neural tissue, like any other physical system, is subjected to several restrictions and boundaries of operations. Here, we proposed a new, bottom-up conceptual paradigm: The Energy Homeostasis Principle, where the balance between energy income, expenditure, and availability are the key parameters in determining the dynamics of neuronal phenomena found from molecular to behavioral levels. Neurons display high energy consumption relative to other cells, with metabolic consumption of the brain representing 20% of the whole-body oxygen uptake, contrasting with this organ representing only 2% of the body weight. Also, neurons have specialized surrounding tissue providing the necessary energy which, in the case of the brain, is provided by astrocytes. Moreover, and unlike other cell types with high energy demands such as muscle cells, neurons have strict aerobic metabolism. These facts indicate that neurons are highly sensitive to energy limitations, with Gibb's free energy dictating the direction of all cellular metabolic processes. From this activity, the largest energy, by far, is expended by action potentials and post-synaptic potentials; therefore, plasticity can be reinterpreted in terms of their energy context. Consequently, neurons, through their synapses, impose energy demands over post-synaptic neurons in a close loop-manner, modulating the dynamics of local circuits. Subsequently, the energy dynamics end up impacting the homeostatic mechanisms of neuronal networks. Furthermore, local energy management also emerges as a neural population property, where most of the energy expenses are triggered by sensory or other modulatory inputs. Local energy management in neurons may be sufficient to explain the emergence of behavior, enabling the assessment of which properties arise in neural circuits and how. Essentially, the proposal of the Energy Homeostasis Principle is also readily testable for simple neuronal networks.

Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate in multivesicular bodies of parent cells and are secreted by fusion of the multivesicular body limiting membrane with the plasma membrane. Their molecular cargo, consisting of RNA species, proteins, and lipids, is in part cell type and cell state specific. Among the RNA species transported by exosomes, microRNAs (miRNAs) are able to modify gene expression in recipient cells. Several miRNAs present in astrocytes are regulated under pathological conditions, and this may have far-reaching consequences if they are loaded in exosomes. We propose that astrocyte-derived miRNA-loaded exosomes, such as miR-26a, are dysregulated in several central nervous system diseases; thus potentially controlling neuronal morphology and synaptic transmission through validated and predicted targets. Unraveling the contribution of this new signaling mechanism to the maintenance and plasticity of neuronal networks will impact our understanding on the physiology and pathophysiology of the central nervous system.

The diagnosis of major depressive disorder (MDD) and bipolar disorder (BD) relies on symptom-based evaluations. Both MDD as well as BD present episodes of depressed mood, often leading to misdiagnosis and treatment delays. Our study presents a novel deep learning–based diagnostic approach that employs microglial cells as biosensors to identify disease-specific image features induced by patient-derived plasma small extracellular vesicles (sEVs), enabling differentiation among MDD, BD, and control (CTRL) groups. Microglial morphological changes in response to plasma sEVs were captured using fluorescence microscopy. Individual cell images were grouped into structured M×M arrays and processed through a DenseNet121 convolutional neural network (CNN). To enhance classification robustness, P image arrays per subject were generated using random cell image permutations and affine transformations. Final diagnoses were assigned through weighted voting across all arrays. Model performance was assessed using repeated subject-disjoint random splits. The CNN-based image analysis framework accurately distinguished between MDD, BD, and CTRL subjects. The best model configuration correctly classified 44 out of 45 individuals across the five cross-validations. By combining deep learning and microglial cell-based biosensing, our results support the proof-of-concept for building a novel diagnostic platform for the differential diagnosis between MDD and BD.

Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity; and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023), addressing their neuroprotective activity in vitro and in vivo.

Methadone is a synthetic long-acting opioid that is increasingly used in the replacement therapy of opioid-addicted patients, including pregnant women. However, methadone therapy in this population poses challenges, as it induces cognitive and behavioral impairments in infants exposed to this opioid during prenatal development. In animal models, prenatal methadone exposure results in detrimental consequences to the central nervous system, such as: (i) increased neuronal apoptosis; (ii) disruption of oligodendrocyte maturation and increased apoptosis and (iii) increased microglia and astrocyte activation. However, it remains unclear whether these deleterious effects result from a direct effect of methadone on brain cells. Therefore, our goal was to uncover the impact of methadone on single brain cell types in vitro. Primary cultures of rat neurons, oligodendrocytes, microglia, and astrocytes were treated for three days with 10 µM methadone to emulate a chronic administration. Apoptotic neurons were identified by cleaved caspase-3 detection, and synaptic density was assessed by the juxtaposition of presynaptic and postsynaptic markers. Apoptosis of oligodendrocyte precursors was determined by cleaved caspase-3 detection. Oligodendrocyte myelination was assessed by immunofluorescence, while microglia and astrocyte proinflammatory activation were assessed by both immunofluorescence and RT-qPCR. Methadone treatment increased neuronal apoptosis and reduced synaptic density. Furthermore, it led to increased oligodendrocyte apoptosis and a reduction in the myelinating capacity of these cells, and promoted the proinflammatory activation of microglia and astrocytes. We showed that methadone, the most widely used drug in opioid replacement therapy for pregnant women with opioid addiction, directly impairs brain cells in vitro, highlighting the need for developing alternative therapies to address opioid addiction in this population.

Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

Repetitive stress negatively affects several brain functions and neuronal networks. Moreover, adult neurogenesis is consistently impaired in chronic stress models and in associated human diseases such as unipolar depression and bipolar disorder, while it is restored by effective antidepressant treatments. The adult neurogenic niche contains neural progenitor cells in addition to amplifying progenitors, neuroblasts, immature and mature neurons, pericytes, astrocytes, and microglial cells. Because of their particular and crucial position, with their end feet enwrapping endothelial cells and their close communication with the cells of the niche, astrocytes might constitute a nodal point to bridge or transduce systemic stress signals from peripheral blood, such as glucocorticoids, to the cells involved in the neurogenic process. It has been proposed that communication between astrocytes and niche cells depends on direct cell-cell contacts and soluble mediators. In addition, new evidence suggests that this communication might be mediated by extracellular vesicles such as exosomes, and in particular, by their miRNA cargo. Here, we address some of the latest findings regarding the impact of stress in the biology of the neurogenic niche, and postulate how astrocytic exosomes (and miRNAs) may play a fundamental role in such phenomenon.

Fluoxetine, the prototypical selective serotonin reuptake inhibitor (SSRI), is widely used to treat major depressive disorder (MDD) and a variety of other central nervous system conditions, primarily due to its established clinical safety profile. Although its efficacy in treating depression is well-recognized, the impact of fluoxetine on cognitive functions remains inconsistent and elusive. In this review, we first examine the well-substantiated biological mechanisms underlying fluoxetine’s antidepressant effects, which include serotonin reuptake inhibition and activation of TrkB receptors—key to brain-derived neurotrophic factor (BDNF) signaling. Subsequently, we delve into the cognitive side effects observed in both preclinical and clinical studies, affecting domains such as memory, attention, and executive functions. While certain studies indicate cognitive improvements in patients with underlying disorders, there is also evidence of negative effects, influenced by variables like gender, duration of treatment, age, disease pathology, and the specifics of cognitive testing. Significantly, the negative cognitive outcomes reported in preclinical research often involve healthy, non-diseased animals. This review underscores the necessity for heightened caution in fluoxetine prescription and further investigation into its potentially detrimental cognitive effects, even when used prophylactically.

Background Maternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as “stress signals” in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues. Results Our mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs. Conclusion Our results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes.