Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3 h a day for 10 days. When adults, these animals were divided into groups and submitted to treatment for 14 days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Dementia and depression: Biological connections with amyloid ß protein.

Dementia is an umbrella term for a broad group of age-associated neurodegenerative diseases. It is estimated that dementia affects 50 million people worldwide and that Alzheimer's disease (AD) is responsible for up to 75% of cases. Small extracellular senile plaques composed of filamentous aggregates of amyloid ß (Aß) protein tend to bind to neuronal receptors, affecting cholinergic, serotonergic, dopaminergic and noradrenergic neurotransmission, leading to neuroinflammation, among other pathophysiologic processes and subsequent neuronal death, followed by dementia. The amyloid cascade hypothesis points to a pathological process in the cleavage of the amyloid precursor protein (APP), resulting in pathological Aß. There is a close relationship between the pathologies that lead to dementia and depression. It is estimated that depression is prevalent in up to 90% of individuals diagnosed with Parkinson's disease, with varying severity, and in 20 to 30% of cases of Alzheimer's disease. The hypothalamic pituitary adrenal (HPA) axis is the great intermediary between the pathophysiological mechanisms in neurodegenerative diseases and depression. This review discusses the role of Aß protein in the pathophysiological mechanisms of dementia and depression, considering the HPA axis, neuroinflammation, oxidative stress, signalling pathways and neurotransmission.

Stress and Kynurenine-Inflammation Pathway in Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most prevalent disorders and causes severe damage to people's quality of life. Lifelong stress is one of the major villains in triggering MDD. Studies have shown that both stress and MDD, especially the more severe conditions of the disorder, are associated with inflammation and neuroinflammation and the relationship to an imbalance in tryptophan metabolism towards the kynurenine pathway (KP) through the enzymes indoleamine-2,3-dioxygenase (IDO), which is mainly stimulated by pro-inflammatory cytokines and tryptophan-2,3-dioxygenase (TDO) which is activated primarily by glucocorticoids. Considering that several pathophysiological mechanisms of MDD underlie or interact with biological processes from KP metabolites, this chapter addresses and discusses the function of these mechanisms. Activities triggered by stress and the hypothalamic-pituitary-adrenal (HPA) axis and immune and inflammatory processes, in addition to epigenetic phenomena and the gut-brain axis (GBA), are addressed. Finally, studies on the function and mechanisms of physical exercise in the KP metabolism and MDD are pointed out and discussed.

COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route.

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.

Impact of COVID-19 in the Mental Health in Elderly: Psychological and Biological Updates.

Since December 2019, the world has been experiencing the challenge of facing coronavirus disease-19 (COVID-19), a severe infectious disease caused by the new coronavirus, SARS-CoV-2. The individuals with the most severe symptoms and the highest risk of death are the elderly and those with chronic illness. Among chronic conditions, those with a certain degree of chronic inflammation may predispose to a more severe evolution of COVID-19. Elderly with psychiatric disorders can present a persistent inflammatory state, a characteristic of the age's immunological senescence, but the disorder can accentuate that. Social isolation is still the safest way to avoid contamination. However, isolated older people may have or worsen mental health conditions due to isolation and health concerns. In this scenario, a SARS-CoV-2 infection may progress to more severe disease. Conversely, COVID-19 can predispose or aggravate psychiatric disorders, as it induces a cytokine storm, causing systemic hyper inflammation. It may damage the blood-brain barrier, resulting in inflammation in the central nervous system. Besides, SARS-CoV-2 is likely to reach and trigger an inflammatory process directly in the nervous system. This review makes an update about research on the mental health of the elderly during the pandemic. Also, it discusses the vulnerability of these individuals in the face of stress and in the case of contracting COVID-19, considering mainly the stress's hormonal and inflammatory mechanisms. Finally, the review points out possible care and attention strategies and entertainment and activities that can reduce the damage to mental and physical health and improve the elderly's quality of life. Graphical abstract Isolation and concerns about COVID-19 may harm elderly mental health. Immunosenescence and pandemic stress increase the risk of psychiatric disorders. Stress and disorders may potentiate the elderly's inflammation and COVID-19 symptoms. SARS-CoV-2 hyperinflammation is a risk factor for elderly psychiatric disorders.