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Effective pharmacotherapy for major depressive disorder remains a major challenge, as more than 30% of patients are resistant to the first line of treatment (selective serotonin reuptake inhibitors) 1 . Sub-anaesthetic doses of ketamine, a non-competitive N -methyl- d -aspartate receptor antagonist 2 , 3 , provide rapid and long-lasting antidepressant effects in these patients 4 – 6 , but the molecular mechanism of these effects remains unclear 7 , 8 . Ketamine has been proposed to exert its antidepressant effects through its metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) 9 . The antidepressant effects of ketamine and (2R,6R)-HNK in rodents require activation of the mTORC1 kinase 10 , 11 . mTORC1 controls various neuronal functions 12 , particularly through cap-dependent initiation of mRNA translation via the phosphorylation and inactivation of eukaryotic initiation factor 4E-binding proteins (4E-BPs) 13 . Here we show that 4E-BP1 and 4E-BP2 are key effectors of the antidepressant activity of ketamine and (2R,6R)-HNK, and that ketamine-induced hippocampal synaptic plasticity depends on 4E-BP2 and, to a lesser extent, 4E-BP1. It has been hypothesized that ketamine activates mTORC1–4E-BP signalling in pyramidal excitatory cells of the cortex 8 , 14 . To test this hypothesis, we studied the behavioural response to ketamine and (2R,6R)-HNK in mice lacking 4E-BPs in either excitatory or inhibitory neurons. The antidepressant activity of the drugs is mediated by 4E-BP2 in excitatory neurons, and 4E-BP1 and 4E-BP2 in inhibitory neurons. Notably, genetic deletion of 4E-BP2 in inhibitory neurons induced a reduction in baseline immobility in the forced swim test, mimicking an antidepressant effect. Deletion of 4E-BP2 specifically in inhibitory neurons also prevented the ketamine-induced increase in hippocampal excitatory neurotransmission, and this effect concurred with the inability of ketamine to induce a long-lasting decrease in inhibitory neurotransmission. Overall, our data show that 4E-BPs are central to the antidepressant activity of ketamine. The antidepressant-like effects of ketamine in mice depend on the expression of specific eIF4E-binding proteins in excitatory and inhibitory neurons.

Previous research has shown that fibroblast growth factor 2 protein (FGF2) can act as an anxiolytic and anti-depressive agent in rodents. Levels of hippocampal FGF2 and FGF2 receptors are decreased in post-mortem brains of individuals with mood disorders. No changes in FGF2 were noted in the post-mortem brains of individuals with mood disorders that were successfully treated with anti-depressant medication prior to death. Mutations in the FGF2 gene in humans have been shown to predict non-responsiveness to the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs). These findings suggest that FGF2 may potentially be a target of and/or required for the therapeutic effects of antidepressant medications. To test this, we employed a rodent model of depressive behaviour, chronic variable stress (CVS) in conjunction with antidepressant treatment (fluoxetine) in wild-type (WT) and FGF2 knockout mice (FGF2KO) and examined depressive and anxiety behaviors. Results showed that fluoxetine reversed the effects of CVS on depressive and anxiety behaviours in wild-type mice only, suggesting that the FGF2 gene is indeed necessary for the therapeutic effects of fluoxetine. Interestingly, CVS decreased hippocampal FGF2 levels and fluoxetine partially reversed this effect. Because FGF2 has been previously shown to modify HPA activity through hippocampal glucocorticoid receptors (GR), we examined levels of glucocorticoid receptors and found a decrease in GR in response to CVS, with a further decrease in FGF2KO. No effect of fluoxetine on GR was observed in either WT or FGF2KO mice. This suggests that further changes in glucocorticoid receptors are not necessary for the anti-depressant effects of fluoxetine in WT mice, although decreased glucocorticoid receptors in response to FGF2 deletion may preclude the therapeutic actions of fluoxetine in FGF2KO. Whether astroglia, astroglial functions, or HPA changes are the downstream target of FGF2-mediated changes induced by fluoxetine remains to be determined, however, the current study reaffirms the potential of FGF2 as a novel therapeutic target in the treatment of depression and anxiety disorders.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that shows considerable heterogeneity of risk factors however, the degree to which race/ethnicity has been actively pursued in PD risk research is unknown. We examined PD literature from 2000–24 and found that less than half accounted for race/ethnicity and only 4.8% of n  = 1142 articles included ethno-racial factors as an integral part of the analysis. This demonstrates that race/ethnicity has been critically understudied in PD and further studies that examine ethno-racial contributions to risk for PD are warranted.

The neuroplasticity hypothesis of depression proposes that major depressive disorders are related to decreased hippocampal and cortical neural plasticity, which is reversed by antidepressant treatment. Astroglial cells have emerged as key mediators of neural plasticity and are involved in the cause and treatment of depression and anxiety-like behaviors. One of the ways that astroglia modulate neuroplasticity is through the formation and maintenance of perineuronal nets (PNNs). Perineuronal nets are important extracellular matrix components that respond to stress and are implicated in anxiety-like behaviors. Normally, astroglial cells continuously turnover PNNs by degrading and donating PNN proteins; however, chronic stress slows PNN protein degradation and increases cortical PNN expression overall. In this report, we used weighted gene co-expression network analysis and eigengene analysis to further delineate the pathways and key regulators involved in the astroglial-PNN relationship following chronic stress. Our analyses indicate that chronic variable stress induces the expression of PNNs through inhibition of trophic pathways and key transcription factors in astroglial cells. These data further support the integral role of astroglial cells in the neuroplasticity hypothesis of depression through their modulation of anxiety-like behaviors and PNNs.

Recent studies have suggested that cortical astroglia play an important role in depressive-like behaviors. Potential astroglial contributions have been proposed based on their known neuroplastic functions, such as glutamate recycling and synaptic plasticity. However, the specific mechanisms by which astroglial cells may contribute or protect against a depressive phenotype remain unknown. To delineate astroglial changes that accompany depressive-like behavior, we used astroglial-specific bacTRAP mice exposed to chronic variable stress (CVS) and profiled the astroglial translatome using translating ribosome affinity purification (TRAP) in conjunction with RNAseq. As expected, CVS significantly increased anxiety- and depressive-like behaviors and corticosterone levels and decreased GFAP expression in astroglia, although this did not reflect a change in the total number of astroglial cells. TRAPseq results showed that CVS decreased genes associated with astroglial plasticity: RhoGTPases, growth factor signaling, and transcription regulation, and increased genes associated with the formation of extracellular matrices such as perineuronal nets (PNNs). PNNs inhibit neuroplasticity and astroglia contribute to the formation, organization, and maintenance of PNNs. To validate our TRAPseq findings, we showed an increase in PNNs following CVS. Degradation of PNNs in the prefrontal cortex of mice exposed to CVS reversed the CVS-induced behavioral phenotype in the forced swim test. These data lend further support to the neuroplasticity hypothesis of depressive behaviors and, in particular, extend this hypothesis beyond neuronal plasticity to include an overall decrease in genes associated with cortical astroglial plasticity following CVS. Further studies will be needed to assess the antidepressant potential of directly targeting astroglial cell function in models of depression.

Psychosocial interventions are an essential part of the treatment for people with severe mental illness such as schizophrenia. The criteria regarding what makes an intervention “evidence-based” along with a current list of evidence-based interventions are presented. Although many evidence-based interventions exist, implementation studies reveal that few, if any, are ever implemented in a given setting. Various theories and approaches have been developed to better understand and overcome implementation obstacles. Among these, merging two evidence-based interventions, or offering an evidence-based intervention within an evidence-based service, are increasingly being reported and studied in the literature. Five such merges are presented, along with their empirical support: cognitive behavior therapy (CBT) with skills training; CBT and family psychoeducation; supported employment (SE) and skills training; SE and cognitive remediation; and SE and CBT.

Purpose - The purpose of this paper is to discuss the design and implementation of an information literacy program for the Faculties of Science and Engineering at McGill University.Design methodology approach - Borrowing from the literature and Bloom's Taxonomy of Educational Objectives, a theoretical approach to audience characterization is used to generate learning outcomes aligned with American Library Association Information Literacy Standards for Science and Technology.Findings - Results suggest that a learner-centered program, addressing potential gaps between perceived and actual skills and needs, is well-received by the student population.Originality value - This study, primarily focused on the description of a program, provides timely and useful information to academic librarians.

The main objective of this thesis was to explore the personal development of youth at risk of delinquency and dropout through their involvement in a psychosocial intervention program named \"Bien dans mes baskets\" (BdmB). This program uses extracurricular basketball as an intervention tool among youth facing various difficulties. It is worth noting that almost all the coaches have professional training in social work or related fields. This thesis presents the results of three studies as parts of a broader research project dealing with the evaluation of the BdmB program. The first study explored the transfer process of the life skills targeted by the BdmB program to other activity fields. Semi-structured interviews were conducted with 14 men and seven women former athlete-students. Our results suggest that, throughout the adult life, three main factors seem to have played a role in the transfer process involving life skills developed as part of BdmB, namely the presence of contexts favoring experiential learning, the relative value granted to the different activity fields and the life trajectory. Our data also shows that beyond the transfer process on an individual scale, a transfer can also occur within the community. The aim of the second study was to explore how participation in BdmB could foster the process of empowerment. Semi-structured interviews were conducted with seven former female participants of BdmB. Our results suggest that a team sport can lead to empowerment through positive socialization, especially when combined with psychosocial intervention. This improvement was most likely the result of cumulative learning experiences including the development and transfer of life skills, the capacity to resist negative external influences as well as the positive impact of experiences in BdmB on their academic aspirations and persistence. The aim of the third study was to evaluate the impact of BdmB program on sense of belonging to school and the presence of social support. A quasi-experimental design was used to evaluate the impact of the program among current participants. The intervention group consisted of the athlete-students of BdmB and the comparison groups consisted of the students from the same school who are not participating in the program, and taking into account whether they are involved or not in sport participation. Individuals were surveyed two times using a self-administered questionnaire over a period of two academic years. Results indicate that the intervention group has developed a better sense of belonging to school and has a better social support compared to comparison groups.

Team sports may represent an arena in which adolescent girls can develop skills and abilities to gain control over their lives. The aim of this retrospective study was to explore how participation in a psychosocial programme using sport as an intervention tool could foster the process of empowerment in young women at risk of delinquency and school dropout. Interviews were conducted with seven young women who were involved in the programme during high school. A descriptive content analysis suggests that involvement in the programme may contribute to the participants' empowerment process through better academic persistency, capacity to resist negative external influences and the development of life skills. Results, however, indicate that the empowerment process is moderated by the participants' differential social environment and life trajectory after high school. (Autor).

Optogenetic stimulation of nigral astrocytes attenuates motor deficits & Th+ cell loss in a 6-OHDA model of neurodegeneration Bulk RNA-seq analysis reveals optogenetic stimulation of nigral astrocytes induces early changes in microglia snRNA-seq shows 6-OHDA alone induces extensive gene expression changes across all cell populations within the SN Oligodendrocytes within the SNc express Th, which is upregulated with DA neuron loss Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra. Glial-glial crosstalk is essential for maintaining the regional milieu, and appears to be particularly important in modulating neuroinflammation and many aspects of neurodegeneration. In particular, astrocytes are critical for maintaining dopamine neuronal integrity and survival, and astroglial dysfunction is prominent in Parkinson’s disease. As such, astrocytes represent a potentially critical therapeutic target in neurodegeneration. In this study, in vivo optogenetics were used to selectively stimulate astrocytes in the substantia nigra following a striatal 6-OHDA lesion. Remarkably, a single bout of optogenetic stimulation was sufficient to attenuate motor deficits and dopamine neuron loss induced by the neurotoxin. Furthermore, bulk RNA-seq and snRNA-seq analysis of the substantia nigra revealed extensive changes in both microglia and oligodendrocytes, suggesting that the neuroprotective effects of stimulating astrocytes may be mediated through alterations in glia-glia crosstalk. Altogether, this work demonstrates the importance of understanding glia-glia interactions in neurodegeneration.