RESUMO
Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis.
RESUMO
OBJECTIVE: Significant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants. METHODS: At the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done. The average decrease in HAMD score was 76.89%. Plasma miR expression profiling was performed by real time PCR. The lists of up-regulated (cut-off=2) and down-regulated miRs were imported into the miRWalk2.0 algorithm and used for target predictions. KEGG database pathways analysis was used to retrieve the pathways significantly targeted by at least two of the miRs. RESULTS: Of the 222 miRs detected in plasma samples of MDD patients, 40 were differentially expressed after treatment. Twenty-three miRs were significantly overexpressed with fold changes between 1.85 and 25.42, and 17 miRs were significantly downregulated with fold changes from 0.28 to 0.68. Pathway analysis revealed a list of 29 pathways for up-regulated miRs, and 20 pathways for down-regulated miRs. Six dysregulated miRs are common to all the top five pathways (Wnt signaling, Cancer, Endocytosis, Axon guidance, MAPK signaling): miR-146a-5p, miR-146b-5p, miR-221-3p, miR-24-3p, miR-26a-5p. CONCLUSION: Overall, our miRWalk analysis of changes in plasma microRNAs after treatment of patients with major depression might open a new avenue for the understanding of Escitalopram mode of action and for its side effects.
