Depression is a prevalent, complex, and highly debilitating disease. The full comprehension of this disease is still a global challenge. Indeed, relapse, recurrency, and therapeutic resistance are serious challenges in the fight against depression. Nevertheless, abnormal functioning of the stress response, inflammatory processes, neurotransmission, neurogenesis, and synaptic plasticity are known to underlie the pathophysiology of this mental disorder. The role of oxidative stress in disease and, particularly, in depression is widely recognized, being important for both its onset and development. Indeed, excessive generation of reactive oxygen species and lack of efficient antioxidant response trigger processes such as inflammation, neurodegeneration, and neuronal death. Keeping in mind the importance of a detailed study about cellular and molecular mechanisms that are present in depression, this review focuses on the link between oxidative stress and the stress response, neuroinflammation, serotonergic pathways, neurogenesis, and synaptic plasticity’s imbalances present in depression. The study of these mechanisms is important to lead to a new era of treatment and knowledge about this highly complex disease.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a significant role in the survival and development of neurons, being involved in several diseases such as Alzheimer’s disease and major depression disorder. The association between BDNF and major depressive disorder is the subject of extensive research. Indeed, numerous studies indicate that decreased levels of BDNF are linked to an increased occurrence of depressive symptoms, neuronal loss, and cortical atrophy. Moreover, it has been observed that antidepressive therapy can help restore BDNF levels. In this review, we will focus on the role of BDNF in major depression disorder serotonergic imbalance and associated stress conditions, particularly hypothalamic–pituitary–adrenal (HPA) axis dysregulation and oxidative stress. All of these features are highly connected to BDNF signaling pathways in the context of this disease, and exploring this topic will aim to advance our understanding of the disorder, improve diagnostic and treatment approaches, and potentially identify new therapeutic targets to alleviate the heavy burden of depression on society.

Several central nervous system (CNS) drugs exhibit potent anti-cancer activities. This study aimed to design a novel model of combination that combines different CNS agents and antineoplastic drugs (5-fluorouracil (5-FU) and paclitaxel (PTX)) for colorectal and breast cancer therapy, respectively. Cytotoxic effects of 5-FU and PTX alone and in combination with different CNS agents were evaluated on HT-29 colon and MCF-7 breast cancer cells, respectively. Three antimalarials alone and in combination with 5-FU were also evaluated in HT-29 cells. Different schedules and concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay, Bliss Independence and HSA methods. Our results demonstrate that fluphenazine, fluoxetine and benztropine have enhanced anticancer activity when used alone as compared to being used in combination, making them ideal candidates for drug repurposing in colorectal cancer (CRC). Regarding MCF-7 cells, sertraline was the most promising candidate alone for drug repurposing, with the lowest IC₅₀ value. For HT-29 cells, the CNS drugs sertraline and thioridazine in simultaneous combination with 5-FU demonstrated the strongest synergism among all combinations. In MCF-7 breast cancer cells, the combination of fluoxetine, fluphenazine and benztropine with PTX resulted in synergism for all concentrations below IC₅₀. We also found that the antimalarial artesunate administration prior to 5-FU produces better results in reducing HT-29 cell viability than the inverse drug schedule or the simultaneous combination. These results demonstrate that CNS drugs activity differs between the two selected cell lines, both alone and in combination, and support that some CNS agents may be promising candidates for drug repurposing in these types of cancers. Additionally, these results demonstrate that 5-FU or a combination of PTX with CNS drugs should be further evaluated. These results also demonstrate that antimalarial drugs may also be used as antitumor agents in colorectal cancer, besides breast cancer.

There is recognition that both stress and immune responses are important factors in a variety of neurological disorders. Moreover, there is an important role of several neurotransmitters that connect these factors to several neurological diseases, with a special focus in this paper on serotonin. Accordingly, it is known that imbalances in stressors can promote a variety of neuropsychiatric or neurodegenerative pathologies. Here, we discuss some facts that link major depressive disorder, Alzheimer’s, and Parkinson’s to the stress and immune responses, as well as the connection between these responses and serotonergic signaling. These are important topics of investigation which may lead to new or better treatments, improving the life quality of patients that suffer from these conditions.

High-caloric diets induce several deleterious alterations in the human body, including the brain. However, information on the effects of these diets on the elderly brain is scarce. Therefore, we studied the effects of 2 months of treatment with high-fat (HF) and high-fat-high-sugar (HFHS) diets on aged male Wistar rats at 18 months. Anxiety levels were analyzed using the open-field and plus-maze tests, while learning and memory processes were analyzed using the Morris water maze test. We also analyzed neurogenesis using doublecortin (DCX) and neuroinflammation using glial fibrillary acidic protein (GFAP). In aged rats, the HFHS diet impaired spatial learning, memory, and working memory and increased anxiety levels, associated with a reduction in the number of DCX cells and an increase in GFAP cells in the hippocampus. In contrast, the effects of the HF diet were lighter, impairing spatial memory and working memory, and associated with a reduction in DCX cells in the hippocampus. Thus, our results suggest that aged rats are highly susceptible to high-caloric diets, even if they only started in the elderly, with an impact on cognition and emotions. Furthermore, diets rich in saturated fats and sugar are more detrimental to aged rats than high-fat diets are.