Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Repetitive transcranial magnetic stimulation and fluoxetine reverse depressive-like behavior but with differential effects on Olig2-positive cells in chronically stressed mice.

Depression is a mood disorder coursing with several behavioral, cellular, and neurochemical alterations. The negative impact of chronic stress may precipitate this neuropsychiatric disorder. Interestingly, downregulation of oligodendrocyte-related genes, abnormal myelin structure, and reduced numbers and density of oligodendrocytes in the limbic system have been identified in patients diagnosed with depression, but also in rodents exposed to chronic mild stress (CMS). Several reports have emphasized the importance of pharmacological or stimulation-related strategies in influencing oligodendrocytes in the hippocampal neurogenic niche. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as an intervention to revert depression. Here, we hypothesized that 5 Hz (Hz) of rTMS or Fluoxetine (Flx) would revert depressive-like behaviors by influencing oligodendrocytes and revert neurogenic alterations caused by CMS in female Swiss Webster mice. Our results showed that 5 Hz rTMS or Flx revert depressive-like behavior. Only rTMS influenced oligodendrocytes by increasing the number of Olig2-positive cells in the hilus of the dentate gyrus and the prefrontal cortex. However, both strategies exerted effects on some events of the hippocampal neurogenic processes, such as cell proliferation (Ki67-positive cells), survival (CldU-positive cells), and intermediate stages (doublecortin-positive cells) along the dorsal-ventral axis of this region. Interestingly, the combination of rTMS-Flx exerted antidepressant-like effects, but the increased number of Olig2-positive cells observed in mice treated only with rTMS was canceled. However, rTMS-Flx exerted a synergistic effect by increasing the number of Ki67-positive cells. It also increased the number of CldU- and doublecortin-positive cells in the dentate gyrus. Our results demonstrate that 5 Hz rTMS has beneficial effects, as it reverted depressive-like behavior by increasing the number of Olig2-positive cells and reverting the decrement in hippocampal neurogenesis in CMS-exposed mice. Nevertheless, the effects of rTMS on other glial cells require further investigation.

5 Hz of repetitive transcranial magnetic stimulation improves cognition and induces modifications in hippocampal neurogenesis in adult female Swiss Webster mice.

Adult hippocampal neurogenesis is regulated by several stimuli to promote the creation of a reserve that may facilitate coping with environmental challenges. In this regard, repetitive transcranial magnetic stimulation (rTMS), a neuromodulation therapy, came to our attention because in clinical studies it reverts behavioral and cognitive alterations related to changes in brain plasticity. Some preclinical studies emphasize the need to understand the underlying mechanism of rTMS to induce behavioral modifications. In this study, we investigated the effects of rTMS on cognition, neurogenic-associated modifications, and neuronal activation in the hippocampus of female Swiss Webster mice. We applied 5 Hz of rTMS twice a day for 14 days. Three days later, mice were exposed to the behavioral battery. Then, brains were collected and immunostained for Ki67-positive cells, doublecortin-positive (DCX+)-cells, calbindin, c-Fos and FosB/Delta-FosB in the dentate gyrus. Also, we analyzed mossy fibers and CA3 with calbindin immunostaining. Mice exposed to rTMS exhibited cognitive improvement, an increased number of proliferative cells, DCX cells, DCX cells with complex dendrite morphology, c-Fos and immunoreactivity of FosB/Delta-FosB in the granular cell layer. The volume of the granular cell layer, mossy fibers and CA3 in rTMS mice also increased. Interestingly, cognitive improvement correlated with DCX cells with complex dendrite morphology. Also, those DCX cells and calbindin immunoreactivity correlated with c-Fos in the granular cell layer. Our results suggest that 5 Hz of rTMS applied twice a day modify cell proliferation, doublecortin cells, mossy fibers and enhance cognitive behavior in healthy female Swiss Webster mice.

The Mexican magnetic resonance imaging dataset of patients with cocaine use disorder: SUDMEX CONN.

Cocaine use disorder (CUD) is a substance use disorder (SUD) characterized by compulsion to seek, use and abuse of cocaine, with severe health and economic consequences for the patients, their families and society. Due to the lack of successful treatments and high relapse rate, more research is needed to understand this and other SUD. Here, we present the SUDMEX CONN dataset, a Mexican open dataset of 74 CUD patients (9 female) and matched 64 healthy controls (6 female) that includes demographic, cognitive, clinical, and magnetic resonance imaging (MRI) data. MRI data includes: 1) structural (T1-weighted), 2) multishell high-angular resolution diffusion-weighted (DWI-HARDI) and 3) functional (resting state fMRI) sequences. The repository contains unprocessed MRI data available in brain imaging data structure (BIDS) format with corresponding metadata available at the OpenNeuro data sharing platform. Researchers can pursue brain variability between these groups or use a single group for a larger population sample.

Mental health problems among healthcare workers involved with the COVID-19 outbreak

Objective: The mental health problems and perceived needs of healthcare workers involved with coronavirus disease (COVID-19) may vary due to individual and contextual characteristics. The objective of this study was to evaluate healthcare workers' mental health problems during the common COVID-19 exposure scenario in Mexico, comparing those on the frontline with other healthcare workers according to gender and profession, determining the main risk factors for the most frequent mental health problems. Methods: A cross-sectional online study was conducted with a non-probabilistic sample of 5,938 Mexican healthcare workers who completed brief screening measures of mental health problems and ad hoc questions about sociodemographic professional characteristics, conditions related to increased risk of COVID-19 infection, life stressors during the COVID-19 emergency, and perceived need to cope with COVID-19. Results: The identified mental health problems were insomnia, depression, and posttraumatic stress disorder (PTSD), all of which were more frequent in frontline healthcare workers (52.1, 37.7, and 37.5%, respectively) and women (47.1, 33.0 %, and 16.3%, respectively). A lack of rest time was the main risk factor for insomnia (OR = 3.1, 95%CI 2.6-3.7, p ≤ 0.0001). Mourning the death of friends or loved ones due to COVID-19 was the main risk factor for depression (OR = 2.2, 95%CI 1.8-2.7, p ≤ 0.0001), and personal COVID-19 status was the main risk factor for PTSD (OR = 2.2, 95%CI 1.7-2.9, p ≤ 0.0001). Conclusion: The most frequent mental health problems during the common exposure scenario for COVID-19 in Mexico included the short-term psychological consequences of intense adversity. A comprehensive strategy for preventing mental health problems should focus on individuals with cumulative vulnerability and specific risk factors.

Mental health problems among healthcare workers involved with the COVID-19 outbreak.

OBJECTIVE: The mental health problems and perceived needs of healthcare workers involved with coronavirus disease (COVID-19) may vary due to individual and contextual characteristics. The objective of this study was to evaluate healthcare workers' mental health problems during the common COVID-19 exposure scenario in Mexico, comparing those on the frontline with other healthcare workers according to gender and profession, determining the main risk factors for the most frequent mental health problems. METHODS: A cross-sectional online study was conducted with a non-probabilistic sample of 5,938 Mexican healthcare workers who completed brief screening measures of mental health problems and ad hoc questions about sociodemographic professional characteristics, conditions related to increased risk of COVID-19 infection, life stressors during the COVID-19 emergency, and perceived need to cope with COVID-19. RESULTS: The identified mental health problems were insomnia, depression, and posttraumatic stress disorder (PTSD), all of which were more frequent in frontline healthcare workers (52.1, 37.7, and 37.5%, respectively) and women (47.1, 33.0 %, and 16.3%, respectively). A lack of rest time was the main risk factor for insomnia (OR = 3.1, 95%CI 2.6-3.7, p ≤ 0.0001). Mourning the death of friends or loved ones due to COVID-19 was the main risk factor for depression (OR = 2.2, 95%CI 1.8-2.7, p ≤ 0.0001), and personal COVID-19 status was the main risk factor for PTSD (OR = 2.2, 95%CI 1.7-2.9, p ≤ 0.0001). CONCLUSION: The most frequent mental health problems during the common exposure scenario for COVID-19 in Mexico included the short-term psychological consequences of intense adversity. A comprehensive strategy for preventing mental health problems should focus on individuals with cumulative vulnerability and specific risk factors.

Vascular endothelial growth factor influences migration and focal adhesions, but not proliferation or viability, of human neural stem/progenitor cells derived from olfactory epithelium.

In humans, new neurons are continuously added in the olfactory epithelium even in the adulthood. The resident neural stem/progenitor cells (hNS/PCs-OE) in the olfactory epithelium are influenced by several growth factors and neurotrophins. Among these modulators the vascular endothelial growth factor (VEGF) has attracted attention due its implicated in cell proliferation, survival and migration of other type of neural/stem progenitor cells. Interestingly, VEGFr2 receptor expression in olfactory epithelium has been described in amphibians but not in humans. Here we show that VEGFr is expressed in the hNS/PCs-OE. We also investigated the effect of VEGF on the hNS/PCs-OE proliferation, viability and migration in vitro. Additionally, pharmacological approaches showed that VEGF (0.5 ng/ml)-stimulated migration of hNS/PCs-OE was blocked with the compound DMH4, which prevents the activation of VEGFr2. Similar effects were found with the inhibitors for Rac (EHT1864) and p38MAPK (SB203850) proteins, respectively. These observations occurred with changes in focal adhesion contacts. However, no effects of VEGF on proliferation or viability were found in hNS/PCs-OE. Our results suggest that hNS/PCs-OE respond to VEGF involving VEGFr2, Rac and p38MAPK.

Human neural stem/progenitor cells derived from the olfactory epithelium express the TrkB receptor and migrate in response to BDNF.

Neurogenesis constitutively occurs in the olfactory epithelium of mammals, including humans. The fact that new neurons in the adult olfactory epithelium derive from resident neural stem/progenitor cells suggests a potential use for these cells in studies of neural diseases, as well as in neuronal cell replacement therapies. In this regard, some studies have proposed that the human olfactory epithelium is a source of neural stem/progenitor cells for autologous transplantation. Although these potential applications are interesting, it is important to understand the cell biology and/or whether human neural stem/progenitor cells in the olfactory epithelium sense external signals, such as brain-derived neurotrophic factor (BDNF), that is also found in other pro-neurogenic microenvironments. BDNF plays a key role in several biological processes, including cell migration. Thus, we characterized human neural stem/progenitor cells derived from the olfactory epithelium (hNS/PCs-OE) and studied their in vitro migratory response to BDNF. In the present study, we determined that hNS/PCs-OE express the protein markers Nestin, Sox2, Ki67 and ßIII-tubulin. Moreover, the doubling time of hNS/PCs-OE was approximately 38h. Additionally, we found that hNS/PCs-OE express the BDNF receptor TrkB, and pharmacological approaches showed that the BDNF-induced (40ng/ml) migration of differentiated hNS/PCs-OE was affected by the compound K252a, which prevents TrkB activation. This observation was accompanied by changes in the number of vinculin adhesion contacts. Our results suggest that hNS/PCs-OE exhibit a migratory response to BDNF, accompanied by the turnover of adhesion contacts.