Peripheral expression of NPY1R-based heteroreceptor complexes reflects hippocampal neuroimmune status: Novel biomarkers for early Alzheimer's disease detection.

Alzheimer's disease (AD) evolves from a prodromal phase with subtle neuroimmune disturbances to overt cognitive decline and hippocampal neurodegeneration. Detecting these early changes non-invasively remains a critical unmet need. Here we show that the abundance of neuropeptide-Y receptor-type-1 (NPY1R)-based heteroreceptor complexes(NPY1R-GALR2 and NPY1R-TrkB), quantified by proximity ligation assay (PLA), constitutes a peripheral read-out of hippocampal status across two complementary rat models.

Impact of climate and land use/land cover changes on malaria incidence in the Ecuadorian Amazon.

Malaria transmission is influenced by climate and land use/land cover change (LULC). This study examines the impact of climate and LULC on malaria risk in the Ecuadorian Amazon. Weekly malaria surveillance data between 2008 and 2019 from Ecuador's Ministry of Public Health were combined with hydrometeorological and LULC data.

Enhancing Cognitive Functions and Neuronal Growth through NPY1R Agonist and Ketamine Co-Administration: Evidence for NPY1R-TrkB Heteroreceptor Complexes in Rats.

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized.

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.

Enhanced neuronal survival and BDNF elevation via long-term co-activation of galanin 2 (GALR2) and neuropeptide Y1 receptors (NPY1R): potential therapeutic targets for major depressive disorder.

Background: Major Depressive Disorder (MDD) is a prevalent and debilitating condition, necessitating novel therapeutic strategies due to the limited efficacy and adverse effects of current treatments. We explored how galanin receptor 2 (GALR2) and Neuropeptide Y1 Receptor (NPYY1R) agonists, working together, can boost brain cell growth and increase antidepressant-like effects in rats. This suggests new ways to treat Major Depressive Disorder (MDD).

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.

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.

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.

Network Profile: Improving Response to Malaria in the Amazon through Identification of Inter-Community Networks and Human Mobility in Border Regions of Ecuador, Peru, and Brazil.

Objectives: Understanding human mobility's role on malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission.

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.

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.

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.

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.

The mGlu Receptor Protomer-Mediated Dopamine D Receptor Trans-Inhibition Is Dependent on the Adenosine A Receptor Protomer: Implications for Parkinson's Disease.

The adenosine A receptor (AR), dopamine D receptor (DR) and metabotropic glutamate receptor type 5 (mGluR) form AR-DR-mGluR heteroreceptor complexes in living cells and in rat striatal neurons. In the current study, we present experimental data supporting the view that the AR protomer plays a major role in the inhibitory modulation of the density and the allosteric receptor-receptor interaction within the DR-mGluR heteromeric component of the AR-DR-mGluR complex in vitro and in vivo. The AR and mGluR protomers interact and modulate DR protomer recognition and signalling upon forming a trimeric complex from these receptors.

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.

Intranasal Delivery of Galanin 2 and Neuropeptide Y1 Agonists Enhanced Spatial Memory Performance and Neuronal Precursor Cells Proliferation in the Dorsal Hippocampus in Rats.

A need for new therapeutic approaches are necessary for dementia conditions and memory deficits of different origins, such as Alzheimer's disease. There is complex pathophysiological mechanisms involved, affecting adult hippocampal neurogenesis, in which neuropeptides and its neurogenesis regulation seem to participate. Neuropeptide Y(NPY) Y1 receptor (Y1R) and galanin (GAL) receptor 2 (GALR2) interact in brain regions responsible for learning and memory processes, emphasizing the hippocampus.

Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia-Relevance for Mental Diseases.

The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation.

The coming together of allosteric and phosphorylation mechanisms in the molecular integration of A2A heteroreceptor complexes in the dorsal and ventral striatal-pallidal GABA neurons.

The role of adenosine A2A receptor (A2AR) and striatal-enriched protein tyrosine phosphatase (STEP) interactions in the striatal-pallidal GABA neurons was recently discussed in relation to A2AR overexpression and cocaine-induced increases of brain adenosine levels. As to phosphorylation, combined activation of A2AR and metabotropic glutamate receptor 5 (mGluR5) in the striatal-pallidal GABA neurons appears necessary for phosphorylation of the GluA1 unit of the AMPA receptor to take place. Robert Yasuda (J Neurochem 152: 270-272, 2020) focused on finding a general mechanism by which STEP activation is enhanced by increased A2AR transmission in striatal-pallidal GABA neurons expressing A2AR and dopamine D2 receptor.

Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus.

A need for new antidepressants is necessary since traditional antidepressants have several flaws. Neuropeptide Y(NPY) Y1 receptor (NPYY1R) and galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the hippocampus. The current study assesses the antidepressant effects induced by GALR2 and NPYY1R coactivation, together with the evaluation of cell proliferation through 5-Bromo-2'-deoxyuridine expression within the dentate gyrus of the ventral hippocampus (vDG).

Evidence for the existence of A2AR-TrkB heteroreceptor complexes in the dorsal hippocampus of the rat brain: Potential implications of A2AR and TrkB interplay upon ageing.

Adenosine A2A receptors (A2AR) are crucial in facilitating the BDNF action on synaptic transmission in the rat hippocampus primarily upon ageing. Furthermore, it has been suggested that A2AR-Tropomyosin related kinase B receptor (TrkB) crosstalk has a pivotal role in adenosine A2AR-mediated modulation of the BDNF action on hippocampal plasticity. Considering the impact of the above receptors interplay on what concerns BDNF-induced enhancement of synaptic transmission, gaining a better insight into the mechanisms behind this powerful crosstalk becomes of primary interest.

Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia.

In the 1980s and 1990s, the concept was introduced that molecular integration in the Central Nervous System could develop through allosteric receptor-receptor interactions in heteroreceptor complexes presents in neurons. A number of adenosine-dopamine heteroreceptor complexes were identified that lead to the A-D heteromer hypothesis of schizophrenia. The hypothesis is based on strong antagonistic A-D receptor-receptor interactions and their presence in the ventral striato-pallidal GABA anti-reward neurons leading to reduction of positive symptoms.

Existence of FGFR1-5-HT1AR heteroreceptor complexes in hippocampal astrocytes. Putative link to 5-HT and FGF2 modulation of hippocampal gamma oscillations.

The majority of the fibroblast growth factor receptor 1-serotonin 1 A receptor (FGFR1-5-HT1AR) heterocomplexes in the hippocampus appeared to be located mainly in the neuronal networks and a relevant target for antidepressant drugs. Through a neurochemical and electrophysiological analysis it was therefore tested in the current study if astrocytic FGFR1-5-HT1AR heterocomplexes also exist in hippocampus. They may modulate the structure and function of astroglia in the hippocampus leading to possible changes in the gamma oscillations.