Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice.

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia). Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson's trichrome, and periodic acid-Schiff staining. Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia. Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.

Baccharis dracunculifolia DC Consumption Improves Nociceptive and Depressive-like Behavior in Rats with Experimental Osteoarthritis.

Osteoarthritis (OA) persistently activates nociceptors, leading to chronic pain, which is often accompanied by the comorbid development of emotional impairments (anxiety and depression), an effect associated with microgliosis. Baccharis dracunculifolia DC (Asteraceae), a Brazilian edible plant, is an important source of active compounds with anti-inflammatory abilities. Thus, we evaluated its ability to reverse OA-induced nociceptive and emotional-like impairments in osteoarthritic ovariectomized female rats using the kaolin/carrageenan (K/C) model. Four weeks after OA induction, mechanical hyperalgesia was confirmed, and the treatment started. Control animals (SHAMs) were treated with phosphate-buffered saline (PBS), while arthritic animals (ARTHs) either received PBS or B. dracunculifolia 50 mg/kg (Bd50) and 100 mg/kg (Bd100), via gavage, daily for five weeks. At the end of the treatment, anxiety-like behavior was assessed using the Open Field Test (OFT), anhedonia was assessed using the Sucrose Preference Test (SPT), and learned helplessness was assessed using the Forced Swimming Test (FST). After occision, microglia were stained with IBA-1 and quantified in brain sections of target areas (prefrontal cortex, amygdala, and periaqueductal grey matter). Treatment with B. dracunculifolia extract reversed OA-induced mechanical hyperalgesia and partly improved depressive-like behavior in OA animals' concomitant to a decrease in the number of M1 microglia. Our findings suggest that B. dracunculifolia extracts can potentially be used in the food industry and for the development of nutraceuticals and functional foods.

Impact of palliative care at end-of-life Covid-19 patients - a small-scale pioneering experience.

BACKGROUND: In March 2020, the outbreak caused by the SARS-CoV-2 virus was declared a pandemic, resulting in numerous fatalities worldwide. To effectively combat the virus, it would be beneficial to involve professionals who specialize in symptom control for advanced illnesses, working closely with other specialties throughout the illness process. This approach can help manage a range of symptoms, from mild to severe and potentially life-threatening. No studies have been conducted in Portugal to analyse the intervention of Palliative Medicine at the end of life of Covid-19 patients and how it differs from other specialties. This knowledge could help determine the importance of including it in the care of people with advanced Covid-19. OBJECTIVES: The objective of this study is to examine potential differences in the care provided to patients with Covid-19 during their Last Hours and Days of Life (LHDOL) between those who received care from Palliative Medicine doctors and those who did not. METHODS: This is a retrospective cohort study spanning three months (Dec 2020 to Feb 2021), the duration of the Support Unit especially created to deal with Covid-19 patients. The database included clinical files from 181 patients admitted to the Support Unit, 27 of which died from Covid-19. RESULTS: Statistically significant differences were identified in the care provided. Specifically, fewer drugs were administered at the time of death, including drugs for dyspnoea, pain and agitation, suspension of futile devices and use of palliative sedation to control refractory symptoms. CONCLUSIONS: End-of-life care and symptomatic control differ when there's regular follow-up by Palliative Medicine, which may translate less symptomatic suffering and promote a dignified and humane end of life.

Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine.

Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine - a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function.

Genista tridentata Phytochemical Characterization and Biological Activities: A Systematic Review.

Genista tridentata (L.) Willk., known as "prickled broom", is a Leguminosae (Fabaceae) species native to the Iberian Peninsula, Morocco, Algeria, and Tunisia. It is used in folk medicine as an anti-inflammatory, for gastrointestinal and respiratory disorders, rheumatism, and headaches, to lower blood pressure, against hypercholesterolemia and hyperglycemia. This study aimed to systematically review the literature on the bioactivities and phytochemical profile of Genista tridentata to understand its pharmacological potential. For this, four electronic databases (PubMed, GoogleScholar, Repositórios Cientificos de Acesso Aberto de Portugal (RCCAP), and ScienceDirect) were searched from inception up to 31 December 2022. From a total of 264 potentially eligible studies considered for screening, 34 papers were considered eligible for this systematic review. The sampling included 71 extracts, collected mainly in Portugal. Genista tridentata extracts present a high level of flavonoids and phenolic compounds. The flowers and aerial parts of the plant were the most studied, and aqueous extracts were the most used. The results predict a high potential for the application of Genista tridentata as a new source of natural antioxidants and preservatives for the food industry with subsequent health benefits, such as the production of nutraceuticals. Moreover, the results indicate that the plant can be collected at all seasons of the year, which represents a benefit for the industry.

Sucrose preference test: A systematic review of protocols for the assessment of anhedonia in rodents.

Anhedonia is described as a decreased ability to experience rewarding and enjoyable activities, a core symptom of major depressive disorder. The sucrose preference test (SPT) is a widely used and reliable behavioural test to assess anhedonia in rodents, based on a two-bottle choice paradigm. To date, different protocols are in use, inducing variability between researchers and hampering comparisons between studies. We performed a systematic review of the SPT protocols used in 2021 to identify the parameters in which they differ and their potential impact. We searched a total of four databases (PubMed, Scopus, Web of Science and Science Direct), from 1st January 2021 to 31st December 2021, and screened a total of 1066 articles. After screening by title and abstract, a total of 415 articles were included in this review. We extracted and analysed the different procedures used, the type of sweet solution and the habituation, deprivation, and testing protocols. The overall quality of the studies was considered very good, however, SPT protocols were extremely variable between studies with a total of 65 different habituation protocols and 104 combinations of food/water deprivation and preference testing duration. As the SPT is one of the most used tests to assess anhedonia in rodents, this work raises awareness of the great variability in SPT protocols being currently used. Furthermore, we call for standardization in the protocol used, and overall improvement of data reporting of methodologies and results, to increase the consistency between studies and allow a better comparison of results between different labs.

Polyoxazoline-Based Nanovaccine Synergizes with Tumor-Associated Macrophage Targeting and Anti-PD-1 Immunotherapy against Solid Tumors.

Immune checkpoint blockade reaches remarkable clinical responses. However, even in the most favorable cases, half of these patients do not benefit from these therapies in the long term. It is hypothesized that the activation of host immunity by co-delivering peptide antigens, adjuvants, and regulators of the transforming growth factor (TGF)-ß expression using a polyoxazoline (POx)-poly(lactic-co-glycolic) acid (PLGA) nanovaccine, while modulating the tumor-associated macrophages (TAM) function within the tumor microenvironment (TME) and blocking the anti-programmed cell death protein 1 (PD-1) can constitute an alternative approach for cancer immunotherapy. POx-Mannose (Man) nanovaccines generate antigen-specific T-cell responses that control tumor growth to a higher extent than poly(ethylene glycol) (PEG)-Man nanovaccines. This anti-tumor effect induced by the POx-Man nanovaccines is mediated by a CD8+ -T cell-dependent mechanism, in contrast to the PEG-Man nanovaccines. POx-Man nanovaccine combines with pexidartinib, a modulator of the TAM function, restricts the MC38 tumor growth, and synergizes with PD-1 blockade, controlling MC38 and CT26 tumor growth and survival. This data is further validated in the highly aggressive and poorly immunogenic B16F10 melanoma mouse model. Therefore, the synergistic anti-tumor effect induced by the combination of nanovaccines with the inhibition of both TAM- and PD-1-inducing immunosuppression, holds great potential for improving immunotherapy outcomes in solid cancer patients.

Effects of Intermittent Fasting on Regulation of Metabolic Homeostasis: A Systematic Review and Meta-Analysis in Health and Metabolic-Related Disorders.

Intermittent fasting (IF) is an emerging dietetic intervention that has been associated with improved metabolic parameters. Nowadays, the most common IF protocols are Alternate-Day Fasting (ADF) and Time-Restricted Fasting (TRF), but in this review and meta-analysis we have also considered Religious Fasting (RF), which is similar to TRF but against the circadian rhythm. The available studies usually include the analysis of a single specific IF protocol on different metabolic outcomes. Herein, we decided to go further and to conduct a systematic review and meta-analysis on the advantages of different IF protocols for metabolic homeostasis in individuals with different metabolic status, such as with obesity, diabetes mellitus type 2 (T2D) and metabolic syndrome (MetS). Systematic searches (PubMed, Scopus, Trip Database, Web of Knowledge and Embase, published before June 2022) of original articles in peer-review scientific journals focusing on IF and body composition outcomes were performed. Sixty-four reports met the eligibility criteria for the qualitative analysis and forty-seven for the quantitative analysis. Herein, we showed that ADF protocols promoted the major beneficial effects in the improvement of dysregulated metabolic conditions in comparison with TRF and RF protocols. Furthermore, obese and MetS individuals are the most benefited with the introduction of these interventions, through the improvement of adiposity, lipid homeostasis and blood pressure. For T2D individuals, IF impact was more limited, but associated with their major metabolic dysfunctions-insulin homeostasis. Importantly, through the integrated analysis of distinct metabolic-related diseases, we showed that IF seems to differently impact metabolic homeostasis depending on an individual's basal health status and type of metabolic disease.

Comparative neurotoxicity of dietary methylmercury and waterborne inorganic mercury in fish: Evidence of optic tectum vulnerability through morphometric and histopathological assessments.

This work investigated the effects of inorganic mercury (iHg) and methylmercury (MeHg) on the fish optic tectum morphology, viz. in relation to: (i) vulnerability of specific optic tectum layers; (ii) preferential targeting of Hg forms to neurons or glial cells; (iii) comparative toxicity of iHg and MeHg in this brain area that is in the maintenance of several fish behaviors. Two experiments exposing juvenile white seabream (Diplodus sargus) to waterborne iHg [HgCl2 (2 µg L-1)] and dietary MeHg (8.7 µg g-1) were performed, comprising both exposure (7 and 14 days; E7 and E14, respectively) and post-exposure (28 days; PE28) periods. Morphometric assessments were performed using stereological methods where the layers of the optic tectum were outlined, while its area and the number of neurons and glial cells were estimated. A histopathological assessment was also performed per section and per layer of optic tectum. iHg exposure did not trigger the loss of neurons during the exposure periods, while a decrease of glial cells was detected in a single layer of the optic tectum at E14. Differently, upon MeHg exposure, a decrease on the number of neurons and glial cells was found in several layers of optic tectum. In the post-exposure, both Hg forms triggered the loss of neurons, while only MeHg exposure led to a decrease on the number of glia cells. The histopathological assessment pointed out a higher toxicity of MeHg in the optic tectum layers, particularly in the post-exposure period, while no significant alterations were found in fish exposed to iHg. Hg forms targeted preferentially neurons. iHg and MeHg are relevant neurotoxicants to fish, with MeHg exposure leading to a higher toxicity than iHg in the optic tectum. After 28 days of post-exposure, iHg and MeHg neurotoxicity remained prominent, suggesting long-term effects of these toxicants.

Injection of kaolin/carrageenan in the rat knee joint induces progressive experimental knee osteoarthritis.

ABSTRACT: Osteoarthritis (OA), the most common joint disorder worldwide, is characterized by progressive degeneration of articular and periarticular structures, leading to physical and emotional impairments that greatly affect the quality of life of patients. Unfortunately, no therapy has been able to halt the progression of the disease. Owing to the complexity of OA, most animal models are only able to mimic a specific stage or feature of the human disorder. In this work, we demonstrate the intraarticular injection of kaolin or carrageenan leads to the progressive degeneration of the rat's knee joint, accompanied by mechanical hyperalgesia and allodynia, gait impairments (reduced contact area of the affected limb), and radiological and histopathological findings concomitant with the development of human grade 4 OA. In addition, animals also display emotional impairments 4 weeks after induction, namely, anxious and depressive-like behaviour, important and common comorbidities of human OA patients. Overall, prolonging kaolin or carrageenan-induced monoarthritis mimics several important physical and psychological features of human OA in both male and female rodents and could be further applied in long-term studies of OA-associated chronic pain.

Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.

Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords "cancer", "Monocarboxylate transporter 1", "SLC16A1" and "prognosis". Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter's overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor.

Heterogenization of Heteropolyacid with Metal-Based Alumina Supports for the Guaiacol Gas-Phase Hydrodeoxygenation.

Because of the global necessity to decrease CO2 emissions, biomass-based fuels have become an interesting option to explore; although, bio-oils need to be upgraded, for example, by catalytic hydrodeoxygenation (HDO), to reduce oxygen content. This reaction generally requires bifunctional catalysts with both metal and acid sites. For that purpose, Pt-Al2O3 and Ni-Al2O3 catalysts containing heteropolyacids (HPA) were prepared. HPAs were added by two different methods: the impregnation of a H3PW12O40 solution onto the support and a physical mixture of the support with Cs2.5H0.5PW12O40. The catalysts were characterized by powder X-ray diffraction, Infrared, UV-Vis, Raman, X-ray photoelectron spectroscopy and NH3-TPD experiments. The presence of H3PW12O40 was confirmed by Raman, UV-Vis and X-ray photoelectron spectroscopy, while the presence of Cs2.5H0.5PW12O40 was confirmed by all of the techniques. However, HPW was shown to strongly interact with the supports, especially in the case of Pt-Al2O3. These catalysts were tested in the HDO of guaiacol, at 300 °C, under H2 and at atmospheric pressure. Ni-based catalysts led to higher conversion and selectivity to deoxygenated compound values, such as benzene. This is attributed to both a higher metal and acidic contents of these catalysts. Among all tested catalysts, HPW/Ni-Al2O3 was shown to be the most promising, although it suffered a more severe deactivation with time-on-stream.

Yoga for COVID-19: An ancient practice for a new condition - A literature review.

A substantial proportion of people with acute COVID-19 develop post-COVID-19 condition (previously known as long-COVID) characterized by symptoms that persist for months after the initial infection, including neuropsychological sequelae. Post-COVID-19 condition frequency varies greatly according to different studies, with values ranging from 4 to 80% of the COVID-19 patients. Yoga is a psycho-somatic approach that increases physical, mental, emotional and spiritual strength, and connection. Yoga practice enhances innate immunity and mental health, so it can be used as complementary therapy in the COVID-19 treatment, namely the post-COVID-19 condition. In this article, we conducted a literature review on yoga and COVID-19, finding that an intervention comprising asana, pranayama, and meditation may be a strategy of choice for these patients' recovery. However, further studies are needed to show its effectiveness in this, still unknown, context.

Bridging the gap of axonal regeneration in the central nervous system: A state of the art review on central axonal regeneration.

Neuronal regeneration in the central nervous system (CNS) is an important field of research with relevance to all types of neuronal injuries, including neurodegenerative diseases. The glial scar is a result of the astrocyte response to CNS injury. It is made up of many components creating a complex environment in which astrocytes play various key roles. The glial scar is heterogeneous, diverse and its composition depends upon the injury type and location. The heterogeneity of the glial scar observed in different situations of CNS damage and the consequent implications for axon regeneration have not been reviewed in depth. The gap in this knowledge will be addressed in this review which will also focus on our current understanding of central axonal regeneration and the molecular mechanisms involved. The multifactorial context of CNS regeneration is discussed, and we review newly identified roles for components previously thought to solely play an inhibitory role in central regeneration: astrocytes and p75NTR and discuss their potential and relevance for deciding therapeutic interventions. The article ends with a comprehensive review of promising new therapeutic targets identified for axonal regeneration in CNS and a discussion of novel ways of looking at therapeutic interventions for several brain diseases and injuries.

An Insight on the Biomedical Potential of Portuguese Propolis from Gerês.

Osteoarthritis (OA), a progressive degenerative disease of weight-bearing joints, is the second leading cause of disability in the world. Despite all the advances and research over the last years, none of the proposed strategies has been effective in generating functional and long-lasting tissue. Due to the high prevalence of OA and the urgent need for an effective and successful treatment, interest in natural products as anti-inflammatory agents, such as propolis and its components, has emerged. In this work, we estimate the biomedical potential of Portuguese propolis, evaluating the in vitro antioxidant and anti-inflammatory effects of single hydroalcoholic extracts prepared with propolis from Gerês sampled over a five-year period (2011-2015) (G.EE70 and G.EE35). The in vivo and in vitro anti-inflammatory potential of the hydroalcoholic extract of mixtures of the same samples (mG.EE70 and mG.EE35) was evaluated for the first time too. DPPH• radical scavenging and superoxide anion scavenging assays showed the strong antioxidant potential of both hydroalcoholic extracts, either prepared from single propolis samples or from the mixtures of the same samples. Results also revealed an anti-inflammatory effect of mG.EE35, both in vitro by inhibiting BSA denaturation and in vivo in the OA-induced model by improving mechanical hyperalgesia as well as the gait pattern parameters. Results further support the use of propolis blends as a better and more efficient approach to take full advantage of the bioactive potential of propolis.

Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation.

Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto's thyroiditis (HT, n = 18), rheumatoid arthritis (RA, n = 16), or systemic lupus erythematosus (SLE, n = 32), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells (p = 0.0215) and a reduced Tfr/Tfh ratio (p = 0.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh (p = 0.0494 and p = 0.0392, respectively) and Tfr (p = 0.0003 and p = 0.0001, respectively) cells, resulting in an unchanged Tfr/Tfh ratio. Activated PD-1+ICOS+Tfh and CD4+PD-1+CXCR5-Tph cells were raised only in patients with SLE (p = 0.0022 and p = 0.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification.

Micro/mesoporous LTL derived materials for catalytic transfer hydrogenation and acid reactions of bio-based levulinic acid and furanics.

The biomass-derived platform chemicals furfural and 5-(hydroxymethyl)furfural (HMF) may be converted to α-angelica lactone (AnL) and levulinic acid (LA). Presently, LA (synthesized from carbohydrates) has several multinational market players. Attractive biobased oxygenated fuel additives, solvents, etc., may be produced from AnL and LA via acid and reduction chemistry, namely alkyl levulinates and γ-valerolactone (GVL). In this work, hierarchical hafnium-containing multifunctional Linde type L (LTL) related zeotypes were prepared via top-down strategies, for the chemical valorization of LA, AnL and HMF via integrated catalytic transfer hydrogenation (CTH) and acid reactions in alcohol medium. This is the first report of CTH applications (in general) of LTL related materials. The influence of the post-synthesis treatments/conditions (desilication, dealumination, solid-state impregnation of Hf or Zr) on the material properties and catalytic performances was studied. AnL and LA were converted to 2-butyl levulinate (2BL) and GVL in high total yields of up to ca. 100%, at 200°C, and GVL/2BL molar ratios up to 10. HMF conversion gave mainly the furanic ethers 5-(sec-butoxymethyl)furfural and 2,5-bis(sec-butoxymethyl)furan (up to 63% total yield, in 2-butanol at 200°C/24 h). Mechanistic, reaction kinetics and material characterization studies indicated that the catalytic results depend on a complex interplay of different factors (material properties, type of substrate). The recovered-reused solids performed steadily.

Platinum nanoparticle-based microreactors protect against the behavioral and neurobiological consequences of chronic stress exposure.

Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.