Major depressive disorder (MDD) is a neuropsychiatric condition linked to neurotransmitter imbalances, neuroinflammation, and purinergic signaling dysregulation. Emerging evidence suggests that environmental pollutants, such as silica nanoparticles (SiNPs), contribute to neuroinflammatory responses and depressive-like behaviors, though the mechanisms remain unclear. This study investigates the effects of repeated SiNP exposure on depressive-like behaviors and purinergic signaling in the hippocampus of adult male rats. Thirty-six Wistar rats were divided into three groups (control, low-dose SiNP, high-dose SiNP) and received intraperitoneal injections for 28 days. Depressive-like behaviors were assessed using the Forced Swimming Test (FST) and Tail Suspension Test (TST), while the enzymatic activities of ectonucleotidases (E-NTPDase, E-NPP, and ecto-5′-nucleotidase) and ATPase function were measured in hippocampal tissue. Gene expression of purinergic receptors (A2A, P2X7, P2Y2) and ectonucleotidases (CD73, NTPDase 1–3) was analyzed via RT-qPCR, with immunohistochemistry and immunofluorescence assessing CD73 and CD90 protein levels. SiNP exposure significantly increased immobility time in both behavioral tests, indicating depressive-like behavior. It also upregulated ectonucleotidase activity, purinergic receptors (A2A, P2X7, P2Y2), and CD73/CD90 expression, while disrupting ATPase function by decreasing both Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities. These findings suggest that SiNPs induce depressive-like behavior through purinergic pathway dysregulation, promoting neuroinflammation and neurotransmission alterations. Further studies are needed to explore purinergic signaling as a potential therapeutic target in depression.

OBJECTIVE: The primary aim of this study was to further characterize the acute effects of amitriptyline (AMI) and escitalopram (ESC) on serum levels of ghrelin, leptin, cortisol and prolactin in healthy humans. METHODS: Eleven healthy male participants received a single dose of AMI 75 mg, ESC 10 mg, or placebo (PLA) at 9:00 PM in a double blind, randomized, controlled, repeated measures study separated by one week. Fasting morning serum levels (7:00 AM) of ghrelin, leptin, cortisol and prolactin were assessed. RESULTS: A repeated measures multivariate analysis of variance revealed a significant main effect for the factor condition (AMI, ESC, PLA). Subsequent univariate analyses demonstrated significant condition effects for ghrelin and cortisol. Post-hoc analyses demonstrated a significant reduction of ghrelin levels after AMI in comparison to PLA, and a significant reduction of cortisol levels after AMI in comparison to both ESC and PLA. Other contrasts did not reach statistical significance. CONCLUSION: Administration of a single dose of AMI, but not of ESC, leads to a significant reduction in morning serum ghrelin and cortisol levels. No effects on leptin and prolactin levels were observed. The differential impact of AMI and ESC on hormones might contribute to different adverse effect profiles of both substances.
Amitriptyline* ; Citalopram* ; Fasting ; Ghrelin ; Healthy Volunteers* ; Humans ; Hydrocortisone ; Leptin ; Male ; Multivariate Analysis ; Prolactin ; Weight Gain