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.

Mental depression: Relation to different disease status, newer treatments and its association with COVID-19 pandemic (Review).

The present study aimed to review major depression, including its types, epidemiology, association with different diseases status and treatments, as well as its correlation with the current COVID-19 pandemic. Mental depression is a common disorder that affects most individuals at one time or another. During depression, there are changes in mood and behavior, accompanied by feelings of defeat, hopelessness, or even suicidal thoughts. Depression has a direct or indirect relation with a number of other diseases including Alzheimer's disease, stroke, epilepsy, diabetes, cardiovascular disease and cancer. In addition, antidepressant drugs have several side effects including sedation, increased weight, indigestion, sexual dysfunction, or a decrease in blood pressure. Stopping medication may cause a relapse of the symptoms of depression and pose a risk of attempted suicide. The pandemic of COVID-19 has affected the mental health of individuals, including patients, individuals contacting patients and medical staff with a number of mental disorders that may adversely affect the immune ability of their bodies. Some of the drugs currently included in the protocols for treating COVID-19 may negatively affect the mental health of patients. Evidence accumulated over the years indicates that serotonin (5HT) deficiencies and norepinephrine (NE) in the brain can lead to mental depression. Drugs that increase levels of NE and 5HT are commonly used in the treatment of depression. The common reason for mood disorders, including mania and bipolar disease are not clearly understood. It is assumed that hyperactivity in specific parts of the brain and excessive activity of neurotransmitters may be involved. Early diagnosis and developing new treatment strategies are essential for the prevention of the severe consequences of depression. In addition, extensive research should be directed towards the investigation of the mental health disturbances occurring during and/or after COVID-19 infection. This may lead to the incorporation of a suitable antidepressant into the current treatment protocols.