Long-term enhancements in antidepressant efficacy and neurogenesis: Effects of intranasal co-administration of neuropeptide Y 1 receptor (NPY1R) and galanin receptor 2 (GALR2) agonists in the ventral hippocampus.

This study evaluates the sustained antidepressant-like effects and neurogenic potential of a 3-day intranasal co-administration regimen of galanin receptor 2 (GALR2) agonist M1145 and neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31, Pro34]NPY in the ventral hippocampus of adult rats, with outcomes analyzed 3 weeks post-treatment. Utilizing the forced swimming test (FST), we found that this co-administration significantly enhances antidepressant-like behaviors, an effect neutralized by the GALR2 antagonist M871, highlighting the synergistic potential of these neuropeptides in modulating mood-related behaviors. In situ proximity ligation assay (PLA) indicated a significant increase in GALR2/NPYY1R heteroreceptor complexes in the ventral hippocampal dentate gyrus, suggesting a molecular basis for the behavioral outcomes observed. Moreover, proliferating cell nuclear antigen (PCNA) immunolabeling revealed increased cell proliferation in the subgranular zone of the dentate gyrus, specifically in neuroblasts as evidenced by co-labeling with doublecortin (DCX), without affecting quiescent neural progenitors or astrocytes. The study also noted a significant uptick in the number of DCX-positive cells and alterations in dendritic morphology in the ventral hippocampus, indicative of enhanced neuronal differentiation and maturation. These morphological changes highlight the potential of these agonists to facilitate the functional integration of new neurons into existing neural circuits. By demonstrating the long-lasting effects of a brief, 3-day intranasal administration of GALR2 and NPY1R agonists, our findings contribute significantly to the understanding of neuropeptide-mediated neuroplasticity and herald novel therapeutic strategies for the treatment of depression and related mood disorders, emphasizing the therapeutic promise of targeting neurogenesis and neuronal maturation processes.

Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus.

BACKGROUND: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. RESEARCH DESIGN AND METHODS: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i.n.) routes. The Forced Swimming Test (FST) was employed to assess antidepressant-like activity, while in situ Proximity Ligation Assay and immunohistochemistry were used to examine NPY1R/TrkB heteroreceptor complexes and BDNF expression in the ventral dentate gyrus (DG), along with neurogenesis markers. RESULTS: The combined treatment significantly reduced immobility in the FST, indicative of enhanced antidepressant-like effects, correlated with increased formation of NPY1R/TrkB complex and brain-derived neurotrophic factor (BDNF) expression in the ventral DG. These molecular alterations were associated with increased neurogenesis. CONCLUSIONS: The coadministration of an NPY1R agonist and Ketamine in a rodent model demonstrated potentiated antidepressant responses through synergistic neurobiological pathways, including TrkB signaling and hippocampal neurogenesis. This indicates a novel therapeutic strategy for MDD, warranting further clinical investigation to fully understand its implications.

Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition.

Introduction: This study may unveil novel insights into the interactions between neuropeptide Y receptor 1 (NPY1R) and galanin receptor 2 (GALR2), in the dentate gyrus of the dorsal hippocampus, shedding light on their role in neurogenesis and cognitive functions. Existing literature highlights the potential of these interactions in enhancing learning and memory, yet detailed mechanisms remain underexplored. Methods: Utilizing intracerebroventricular injections of GALR2 and NPY1R agonists in Sprague-Dawley male rats, we examined neurogenesis via markers PCNA and DCX, and memory consolidation through the object-in-place task over a three-week period. Results: Significant increases in NPY1R-GALR2 co-localization and neuroblast proliferation were observed, alongside enhanced memory consolidation. These findings suggest a synergistic effect of NPY1R and GALR2 activation on cognitive functions. Discussion: Our findings may foster the development of novel heterobivalent or multitargeting drugs, affecting NPY1R-GALR2 interaction, and suggest a future pharmacogical strategy for improving learning and memory found in many brain diseases. Further research is encouraged to explore these mechanisms in pathological models.

An Insertion Within SIRPß1 Shows a Dual Effect Over Alzheimer's Disease Cognitive Decline Altering the Microglial Response.

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.

Enhancement of neurogenesis and cognition through intranasal co-delivery of galanin receptor 2 (GALR2) and neuropeptide Y receptor 1 (NPY1R) agonists: a potential pharmacological strategy for cognitive dysfunctions.

BACKGROUND: Spatial memory deficits and reduced neuronal survival contribute to cognitive decline seen in the aging process. Current treatments are limited, emphasizing the need for innovative therapeutic strategies. This research explored the combined effects of intranasally co-administered galanin receptor 2 (GALR2) and neuropeptide Y1 receptor (NPY1R) agonists, recognized for their neural benefits, on spatial memory, neuronal survival, and differentiation in adult rats. After intranasal co-delivery of the GALR2 agonist M1145 and a NPY1R agonist to adult rats, spatial memory was tested with the object-in-place task 3 weeks later. We examined neuronal survival and differentiation by assessing BrdU-IR profiles and doublecortin (DCX) labeled cells, respectively. We also used the GALR2 antagonist M871 to confirm GALR2's crucial role in promoting cell growth. RESULTS: Co-administration improved spatial memory and increased the survival rate of mature neurons. The positive effect of GALR2 in cell proliferation was confirmed by the nullifying effects of its antagonist. The treatment boosted DCX-labeled newborn neurons and altered dendritic morphology, increasing cells with mature dendrites. CONCLUSIONS: Our results show that intranasal co-delivery of GALR2 and NPY1R agonists improves spatial memory, boosts neuronal survival, and influences neuronal differentiation in adult rats. The significant role of GALR2 is emphasized, suggesting new potential therapeutic strategies for cognitive decline.

Cognitive, neuropsychiatric and neurological alterations in mastocytosis: A systematic review.

BACKGROUND: Mastocytosis manifests with multisystemic symptoms, often involving the nervous system. Numerous cognitive, neuropsychiatric and neurological alterations have been reported in multiple observational studies. METHODS: We performed a qualitative systematic literature review of reported data consulting the electronic databases Medline, Scopus, Web of Science, Cochrane, and BASE until June 2023. RESULTS: We selected 24 studies in which the majority showed that a high proportion of mastocytosis patients suffer cognitive, neuropsychiatric and neurological alterations. The most common disorders and estimated ranges of frequency observed in adults were depression (68%-75%), anxiety, high stress or irritability (27%-54%), cognitive impairment (27%-39%, primarily affecting memory skills), and headaches (55%-69%). Attention challenges and learning difficulties were reported in children at a rate of 13%, while neurodevelopmental disorders occurred at rates of 8%-12%. Frequent white abnormalities in mastocytosis patients with concomitant psychocognitive symptoms have been reported although neuroimaging studies have been performed rarely in this population. CONCLUSION: Further studies with more comprehensive and homogeneous evaluations and neuroimaging and histological analysis should be performed for a better understanding of these manifestations. An earlier detection and proper management of these symptoms could greatly improve the quality of life of these patients.

Structural and Functional Retinal Changes in Patients with Mild Cognitive Impairment with and without Diabetes.

Our objective is to analyze retinal changes using optical coherence tomography angiography (OCT-A) in patients with mild cognitive impairment (MCI) to characterize structural and vascular alterations. This cross-sectional study involved 117 eyes: 39 eyes from patients with MCI plus diabetes (DM-MCI), 39 eyes from patients with MCI but no diabetes (MCI); and 39 healthy control eyes (C). All patients underwent a visual acuity measurement, a structural OCT, an OCT-A, and a neuropsychological examination. Our study showed a thinning of retinal nerve fiber layer thickness (RNFL) and a decrease in macular thickness when comparing the MCI-DM group to the C group (p = 0.008 and p = 0.016, respectively). In addition, an increase in arteriolar thickness (p = 0.016), a reduction in superficial capillary plexus density (p = 0.002), and a decrease in ganglion cell thickness (p = 0.027) were found when comparing the MCI-DM group with the MCI group. Diabetes may exacerbate retinal vascular changes when combined with mild cognitive impairment.

Psychosocial interventions reduce cortisol in breast cancer patients: systematic review and meta-analysis.

Introduction: Cancer initiation, progression and recurrence are intricate mechanisms that depend on various components: genetic, psychophysiological, or environmental. Exposure to chronic stress includes fear of recurrence that can affect biological processes that regulate immune and endocrine systems, increase cancer risk, and influence the survival rate. Previous studies show that psychological interventions might influence the level of cortisol that has been extensively used as a biomarker for measuring hypothalamic-pituitary-adrenal axis functioning and body's immunity response. This meta-analysis aimed to provide a quantitative scrutiny of the effect of certain types of psychosocial interventions on cortisol as a neuroendocrine biomarker in saliva or blood and might predict breast cancer (BC) progression. Methods: A literature search was performed in the following databases: PubMed, The Cohrane Library, Scopus, WOS, PsychInfo, Google Scholar, Ovid Science Direct. After methodical selection of originally generated 2.021 studies, the search yielded eight articles that met inclusion criteria. All these studies explored effects of psychosocial interventions that measured cortisol in total of 366 participants with BC, stages 0-IV, in randomized control trial or quasi experimental study design setting. We applied random effects model to conduct meta-analyses on the parameters of salivary and plasma cortisol and used PRISMA Guidelines as validated methodology of investigation to report the results. Results: Eight studies selected for meta-analysis have shown the reduction of cortisol level due to applied psychosocial intervention. The random effects model showed that interventions produced large effect sizes in reductions of cortisol in blood (Cohen's d = -1.82, 95% Confidence Interval (CI): -3.03, -0.60) and slightly less in saliva (d = -1.73, 95%CI: -2.68, -0.78) with an overall effect of d = -1.76 (95%CI: -2.46, -1.07). Conclusion: Our study concluded that certain types of psychosocial interventions reduce cortisol (indicator of chronic stress) in patients with BC. Application of specific psychosocial support as adjuvant non-invasive therapy for affected females with BC at all phases of treatment could contribute to more cost-effective health care.

Biomechanical Assessments in Woodwind Musicians: A Systematic Review.

Biomechanical methods are frequently used to provide information about the kinematics and kinetics of posture and movement during musical performance. The aim of this review was to identify and analyze the biomechanical methods performed on woodwind musicians to understand their musculoskeletal demands. A systemic review was carried out following the guidelines of the document Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It was registered in PROSPERO (code 430304).The databases PubMed, Cochrane, CINAHL, Scopus, and Web of Science were consulted between January 2000 and March 2022. The search in the databases identified 1625 articles, and 16 different studies were finally included in the review, with a sample size of 390 participants. Pressure sensors, surface electromyography, infrared thermography, goniometry in two dimensions, and ultrasound topometry in three dimensions were biomechanical methods useful to broaden the knowledge of musculoskeletal demands during musical practice. Piezoresistive pressure sensors were the most widely used method. The great heterogeneity of the studies limited the comparability of the results. The findings raised the need to increase both the quantity and the quality of studies in future research.

Assessing adipokines as potential biomarkers of dementia, Alzheimer's disease, and mild cognitive impairment: A systematic review and meta-analysis.

Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are currently unknown. The answer could lie on the involvement of gastrointestinal factors, such as adipokines (e.g., leptin, adiponectin, and resistin) and ghrelin. In this context, we conducted a pre-registered systematic review and meta-analysis of 42 cross-sectional and 13 longitudinal studies targeting the associations between leptin, adiponectin, resistin, and ghrelin and the prevalence of general dementia, AD, and mild cognitive impairment (MCI). We also examined the relationship between the four gastrointestinal factors and neurocognitive outcomes and AD-related cerebrospinal fluid biomarkers. Patients with AD had lower blood leptin and higher resistin levels than cognitively normal participants. Lower leptin and higher resistin were associated with higher degree of cognitive impairment. Additionally, lower late-life leptin levels might be associated with higher prospective risk of dementia and AD, although more studies are needed to corroborate this. Results in ghrelin and adiponectin were not conclusive, with age, sex distribution, obesity, and severity of dementia seemingly acting as moderators across several analyses. Our work might contribute to the identification of new preclinical blood markers of MCI and AD.

Effects of GLP-1 receptor agonists on neurological complications of diabetes.

Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.

Subclinical atherosclerosis burden in non-diabetic hypertensives treated in primary care center: the IMTABI study.

BACKGROUND: Identifying patients at high risk of cardiovascular disease in primary prevention is a challenging task. This study aimed at detecting subclinical atherosclerosis burden in non-diabetic hypertensive patients in a primary care centre. METHODS: Clinical, anthropometric and analytical data were collected from patients with hypertension who were free from clinical vascular disease and diabetes. The cardiovascular risk was assessed using the SCORE system. Subclinical atherosclerosis burden was assessed by carotid ultrasonography (intima-medial thickness [IMT] and plaque) and measurement of the ankle-brachial index (ABI). RESULTS: Out of 140 patients, 59 (42%) have carotid plaque, 32 (23%) have IMT higher than 75% and 12 (9%) have an ABI < 0.9. Total atherosclerosis burden was present in 91 (65%) of the subjects. Consequently, 59 (42%) patients were re-classified into the very high-risk category. In multivariate analyses, smoking, creatinine levels and duration of hypertension were associated with atherosclerosis burden. In contrast, only smoking and age were associated with the presence of carotid plaque. Almost 90% of patients were treated with hypotensive drugs, half of them combined several drugs and 60% were well-controlled. Only 30% received statins in monotherapy and only less than 20% had an LDL cholesterol < 100 mg/dL. CONCLUSIONS: In non-diabetic hypertensive patients managed at a primary care centre, 4 out of 10 had subclinical atherosclerosis burden and were re-classified into the very high- risk category. There was clear undertreatment with lipid-lowering drugs of most LDL cholesterol inappropriate levels, according to current clinical guidelines.

Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion.

Different brain regions' interactions have been implicated in relevant neurological diseases, such as major depressive disorder (MDD), anxiety disorders, age-dependent cognitive decline, Alzheimer's disease (AD) and addiction. We aim to explore the role of the medial prefrontal cortex (mPFC) in the Neuropeptide Y (NPY) and Galanin (GAL) interaction since we have demonstrated specific NPY and GAL interactions in brain areas related to these brain diseases. We performed GALR2 and Y1R agonists intranasal infusion and analyzed the mPFC activation through c-Fos expression. To assess the associated cellular mechanism we studied the formation of Y1R-GALR2 heteroreceptor complexes with in situ proximity ligation assay (PLA) and the expression of the brain-derived neurotrophic factor (BDNF). Moreover, the functional outcome of the NPY and GAL interaction on the mPFC was evaluated in the novel object preference task. We demonstrated that the intranasal administration of both agonists decrease the medial prefrontal cortex activation as shown with the c-Fos expression. These effects were mediated by the decreased formation of Y1R-GALR2 heteroreceptor complexes without affecting the BDNF expression. The functional outcome of this interaction was related to an impaired performance on the novel object preference task. Our data may suggest the translational development of new heterobivalent agonist pharmacophores acting on Y1R-GALR2 heterocomplexes in the medial prefrontal cortex for the novel therapy on neurodegenerative and psychiatric diseases. DATA SHARING AND DATA ACCESSIBILITY: The data that support the findings of this study are openly available in Institutional repository of the University of Malaga (RIUMA) and from the corresponding author upon reasonable request.

GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions.

Dysregulation of adult hippocampal neurogenesis is linked to major depressive disorder (MDD), with more than 300 million people diagnosed and worsened by the COVID-19 pandemic. Accumulating evidence for neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular-, and behavioral-specific levels. The purpose of the current work was to evaluate the proliferating role of GAL2 receptor (GALR2) and Y1R agonists interaction upon intranasal infusion in the ventral hippocampus. We studied their hippocampal proliferating actions using the proliferating cell nuclear antigen (PCNA) on neuroblasts or stem cells and the expression of the brain-derived neurothrophic factor (BDNF). Moreover, we studied the formation of Y1R-GALR2 heteroreceptor complexes and analyzed morphological changes in hippocampal neuronal cells. Finally, the functional outcome of the NPY and GAL interaction on the ventral hippocampus was evaluated in the forced swimming test. We demonstrated that the intranasal infusion of GALR2 and the Y1R agonists promotes neuroblasts proliferation in the dentate gyrus of the ventral hippocampus and the induction of the neurotrophic factor BDNF. These effects were mediated by the increased formation of Y1R-GALR2 heteroreceptor complexes, which may mediate the neurites outgrowth observed on neuronal hippocampal cells. Importantly, BDNF action was found necessary for the antidepressant-like effects after GALR2 and the Y1R agonists intranasal administration. Our data may suggest the translational development of new heterobivalent agonist pharmacophores acting on Y1R-GALR2 heterocomplexes in the ventral hippocampus for the novel therapy of MDD or depressive-affecting diseases.

Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review.

BACKGROUND: Optical coherence tomography (OCT) has enabled several retinal alterations to be detected in patients with Alzheimer disease (AD), alterations that could be potential biomarkers. However, the relationship between the retina and other biomarkers of AD has been underresearched. We gathered and analyzed the literature about the relationship between retinal and cerebral alterations detected via neuroimaging in patients with AD, mild cognitive impairment (MCI), and preclinical AD. METHODS: This systematic review followed the PRISMA Statement guidelines through the 27 items on its checklist. We searched in PubMed, BVS, Scopus, and the Cochrane Library, using the keywords: Alzheimer's disease, optical coherence tomography, white matter, cortex, atrophy, cortical thickness, neuroimaging, magnetic resonance imaging, and positron emission tomography. We included articles that studied the retina in relation to neuroimaging in patients with AD, MCI, and preclinical AD. We excluded studies without OCT, without neuroimaging, clinical cases, opinion articles, systematic reviews, and animal studies. RESULTS: Of a total of 35 articles found, 23 were finally included. Although mixed results were found, most of these corroborate the relationship between retinal and brain disorders. CONCLUSIONS: More rigorous research is needed in the field, including homogenized, longitudinal, and prolonged follow-up studies, as well as studies that include all stages of AD. This will enable better understanding of the retina and its implications in AD, leading to the discovery of retinal biomarkers that reflect brain alterations in AD patients in an accessible and noninvasive manner.

Insulin-Related Biomarkers in Cerebrospinal Fluid in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review.

BACKGROUND: Glucose metabolism and insulin signaling alterations play an important role in Alzheimer's disease (AD) pathogenesis. Researchers have extensively attempted to characterize the exact pathophysiological mechanisms in the cerebrospinal fluid (CSF), as evidence concerning this fluid biomarkers is expected to enhance AD diagnosis' specificity and accuracy and serve as an early disease detection tool. There is controversy about insulin levels in the CSF relationship with mild cognitive impairment (MCI) and AD. OBJECTIVE: This systematic review provides an overview of the state-of-the-art knowledge about insulin-related CSF biomarkers in AD and MCI. METHODS: We performed a qualitative systematic literature review of reported data of CSF glucose, insulin, or insulin-related molecules in humans with AD or MCI, consulting the electronic databases Medline, Scopus, Web of Science, Cochrane, and BASE until May 2022. RESULTS: We selected 19 studies, 10 of them reporting data on CSF insulin and 8 on insulin-related molecules like growth factors or their binding proteins. They predominantly found decreased levels of CSF insulin and increased levels of CSF insulin-related growth factors and their binding proteins. CONCLUSION: Due to the studies' protocols and results heterogeneity, we recommend a larger database of clinical trials with similar characteristics for a better understanding of this relationship.

Galanin and Neuropeptide Y Interaction Enhances Proliferation of Granule Precursor Cells and Expression of Neuroprotective Factors in the Rat Hippocampus with Consequent Augmented Spatial Memory.

Dysregulation of hippocampal neurogenesis is linked to several neurodegenereative diseases, where boosting hippocampal neurogenesis in these patients emerges as a potential therapeutic approach. Accumulating evidence for a neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular-, and behavioral-specific levels. The purpose of the current work was to evaluate the role of the NPY and GAL interaction in the neurogenic actions on the dorsal hippocampus. We studied the Y1R agonist and GAL effects on: hippocampal cell proliferation through the proliferating cell nuclear antigen (PCNA), the expression of neuroprotective and anti-apoptotic factors, and the survival of neurons and neurite outgrowth on hippocampal neuronal cells. The functional outcome was evaluated in the object-in-place task. We demonstrated that the Y1R agonist and GAL promote cell proliferation and the induction of neuroprotective factors. These effects were mediated by the interaction of NPYY1 (Y1R) and GAL2 (GALR2) receptors, which mediate the increased survival and neurites' outgrowth observed on neuronal hippocampal cells. These cellular effects are linked to the improved spatial-memory effects after the Y1R agonist and GAL co-injection at 24 h in the object-in-place task. Our results suggest the development of heterobivalent agonist pharmacophores, targeting Y1R-GALR2 heterocomplexes, therefore acting on the neuronal precursor cells of the DG in the dorsal hippocampus for the novel therapy of neurodegenerative cognitive-affecting diseases.

Melodic Intonation Therapy in Post-Stroke Non-Fluent Aphasia and Its Effects on Brain Plasticity.

Melodic Intonation Therapy (MIT) is one of the most well-known therapies for the rehabilitation of speech in patients with non-fluent aphasia and which is thought to promote right-hemisphere involvement in language processing. This review focuses on the study of language lateralization and/or neuroplastic reorganization with neuroimaging and/or neurophysiological techniques in non-fluent aphasic patients post-stroke during or after MIT. A systematic search was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) in databases (PubMed, Scopus, EMBASE, Dialnet, Web of Science, Cochrane) with the keywords melodic intonation therapy, neuroimaging, functional magnetic resonance, and positron emission tomography and the boolean operators AND and OR. Articles including patients of all ages and either sex with any type of aphasia post-stroke and in any language, which studied language lateralization and/or neuroplastic reorganization after or during MIT were included. Articles which did not achieve the objectives, revisions and conferences were excluded. Different results were obtained from the 16 studies included in the review: predominantly greater activation of the right hemisphere but also of the left hemisphere or both. MIT is an effective therapy to rehabilitate non-fluent aphasic patients post-stroke. It involves different neurobiological mechanisms and depends on multiple individual factors. Studies with larger samples are necessary.

Evidence of Animal-Assisted Therapy in Neurological Diseases in Adults: A Systematic Review.

BACKGROUND: In recent years, the possibility of intervening humans with animal-assisted therapy (AAT) has been growing due to numerous physical, psychological, and social benefits provided to humanity, enabling them to maintain or improve their quality of life. There exist different animals through which this therapy can be performed. The purpose of this systematic review will focus on the effects of AAT in several neurological diseases. METHODS: The search of clinical trials was carried out in the PubMed, Scielo, Embase and PEDro databases. The selection of articles was made according to the different inclusion and exclusion criteria, incorporating those that approached neurological diseases to be reviewed. RESULTS: Twenty-five clinical trials were identified, seventeen of which were finally included in the review. The results indicate that animal-assisted therapy (AAT) in different neurological diseases has many benefits in several areas, for example, in motor and physical ability as well as in mental and behavioural health. CONCLUSIONS: This systematic review provides occupational therapy practitioners with evidence on the use of activity based on animal-assisted therapy as a novel field of intervention that can complement other therapies and obtain benefits in different populations.