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Abstract: Major Depressive Disorder (MDD) is a common mental illness that causes significant disability and declining quality of life. An overlap of multiple factors can be involved in the pathophysiology of this mood disorder, including increased inflammation and oxidative stress, change in neurotransmitters, decreased brain-derived neurotrophic factor (BDNF), activation of the hypothalamic-pituitary-adrenal (HPA) axis, and changes in the microbiota-gut-brain axis. Although the classic treatment for MDD is safe, it is far from ideal, with delay to start the best clinic, side effects, and a large number of non-responses or partial-responses. Therefore, other alternatives are being studied to improve depressive symptoms, and, among them, the role of phytochemicals present in food stands out. This mini-review will discuss the main phytochemicals present in foods that have clinical and preclinical studies showing benefits for MDD treatment. In addition, the main mechanisms of action that are being proposed for each of these compounds will be addressed.

A suitable enriched environment favors development but can also influence behavior and neuronal circuits throughout development. Studies have shown that environmental enrichment (EE) can be used as an essential tool or combined with conventional treatments to improve psychiatric and neurological symptoms, including major depressive disorder (MDD) and autism spectrum disorder (ASD). Both disorders affect a significant percentage of the wofrld's population and have complex pathophysiology. Moreover, the available treatments for MDD and ASD are still inadequate for many affected individuals. Experimental models demonstrate that EE has significant positive effects on behavioral modulation. In addition, EE has effects on neurobiology, including improvement in synaptic connections and neuroplasticity, modulation of neurotransmissions, a decrease in inflammation and oxidative stress, and other neurobiology effects that can be involved in the pathophysiology of MDD and ASD. Thus, this review aims to describe the leading behavioral and neurobiological effects associated with EE in MDD and ASD.

Abstract: Microglia are immune cells found in the central nervous system (CNS) involved in infection combat and cellular debris clean. These glial cells are involved in synaptogenesis during brain development by their interactions with neurons and other glial cells. These relations are associated with the secretion of signaling molecules, such as chemokines and neurotrophic factors. Microglia cells influence synapsis and neuron morphology during different phases of development. Also, other systems, for example, gut microbiota, indirectly affect microglial functions and morphology. Several factors that can occur in different development periods, including intrauterine through adult life, could impact microglia. Impairment in these cells could be associated with the development of some psychiatric conditions, such as schizophrenia, autistic spectrum disorder (ASD), and depression. This review focuses on describing microglia functions in the maintenance of CNS and how they are associated with other systems, as the gutmicrobiota brain axis and environmental stressors, such as stress, maternal deprivation, sleep deprivation, immune activation, and ethanol exposure, that can influence the function of the microglia during neurodevelopment.

Background: Studies have demonstrated an important impact of systemic inflammation in the central nervous system, which could be related to psychiatric disorders’ pathophysiology. Ketamine can have anti-inflammatory proprieties, but dose-dependently effects need to be studied. Objective: To evaluate the effect of different doses of ketamine on levels of neurotrophins and inflammatory cytokines in the brains of rats. Methods: Wistar rats were submitted to the cecal ligation and puncture (CLP) model of sepsis. Thirty days after the CLP procedure, the rats received an intraperitoneal injection (i.p.) of ketamine (5, 15, or 25 mg/kg) or saline, once a day for seven days. The rats were killed 30 minutes after the last i.p. injection. The frontal cortex, hippocampus, and striatum were dissected for analysis of IL-1𝛽, IL-6, IL-10, TNF-α, BDNF, NGF, NT-3, and GDNF levels. Results: CLP increased the levels of IL-1𝛽, IL-6, IL-10, and TNF-α levels in the frontal cortex and/or hippocampus of rats. Besides, BDNF levels were decreased by CLP in all structures analyzed. NGF and GDNF were decreased only in the hippocampus. Ketamine at 5 mg/kg reversed all alterations caused by CLP and per se increased the levels of BDNF and NGF in the frontal cortex and/or hippocampus. Ketamine at 15 mg/kg increased BDNF and NGF levels. In turn, Ketamine at 25mg/kg potentiates the inflammatory injury on the brain induced by CLP. Conclusion:We suggest that ketamine could work differently in a systemic inflammation environment, and caution needs to be taken depending on the inflammatory history of the patient.

Major depressive disorder (MDD) is the most prevalent mood disorder globally. Most antidepressants available for the treatment of MDD increase the concentration of monoamines in the synaptic cleft. However, such drugs have a high latency time to obtain benefits. Thus, new antidepressants with fast action and robust efficacy are very important. This study evaluated the effects of escitalopram, ketamine, and probiotic Bifidobacterium infantis in rats submitted to the maternal deprivation (MD). MD rats received saline, escitalopram, ketamine, or probiotic for 10, 30, or 50 days, depending on the postnatal day (PND):21, 41, and 61. Following behavior, this study examined the integrity of the blood-brain barrier (BBB) and oxidative stress markers. MD induced depressive-like behavior in females with PND21 and males with PND61. All treatments reversed depressive-like behavior in females and escitalopram and ketamine in males. MD induced an increase in the permeability of the BBB, an imbalance between oxidative stress and antioxidant defenses. Treatments regulated the oxidative damage and the integrity of the BBB induced by MD. The treatment with escitalopram, ketamine, or probiotics may prevent behavioral and neurochemical changes associated with MDD, depending on the developmental period and gender.