Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats.

INTRODUCTION: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex. MATERIALS AND METHODS: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels. RESULTS: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant. CONCLUSION: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.

The role of genetics and gender specific differences in neurodegenerative disorders: Insights from molecular and immune landscape.

Neurodegenerative disorders (NDDs) are the most common neurological disorders with high prevalence and have significant socioeconomic implications. Understanding the underlying cellular and molecular mechanisms associated with the immune system can be effective in disease etiology, leading to more effective therapeutic approaches for both females and males. The central nervous system (CNS) actively participates in immune responses, both within and outside the CNS. Immune system activation is a common feature in NDDs. Gender-specific factors play a significant role in the prevalence, progression, and manifestation of NDDs. Neuroinflammation, in both inflammatory neurological and neurodegenerative conditions, is defined by the triggering of microglia and astrocyte cell activation. This results in the secretion of pro-inflammatory cytokines and chemokines. Numerous studies have documented the role of neuroinflammation in neurological diseases, highlighting the involvement of immune signaling pathways in disease development. Converging evidence support immune system involvement during neurodegeneration in NDDs. In this review, we summarize emerging evidence that reveals gender-dependent differences in immune responses related to NDDs. Also, we highlight sex differences in immune responses and discuss how these sex-specific influences can increase the risk of NDDs. Understanding the role of gender-specific factors can aid in developing targeted therapeutic strategies and improving patient outcomes. Ultimately, the better understanding of these mechanisms contributed to sex-dependent immune response in NDDs, can be critically usful in targeting of immune signaling cascades in such disorders. In this regard, sex-related immune responses in NDDs may be promising and effective targets in therapeutic strategies.

Cognitive Impairment and Neurodegenerative Diseases Development Associated with Organophosphate Pesticides Exposure: a Review Study.

A significant body of literature emphasizes the role of insecticide, particularly organophosphates (OPs), as the major environmental factor in the etiology of neurodegenerative diseases. This review aims to study the relationship between OP insecticide exposure, cognitive impairment, and neurodegenerative disease development. Human populations, especially in developing countries, are frequently exposed to OPs due to their extensive applications. The involvement of various signaling pathways in OP neurotoxicity are reported, but the OP-induced cognitive impairment and link between OP exposure and the pathophysiology of neurodegenerative diseases are not clearly understood. In the present review, we have therefore aimed to come to new conclusions which may help to find protective and preventive strategies against OP neurotoxicity and may establish a possible link between organophosphate exposure, cognitive impairment, and OP-induced neurotoxicity. Moreover, we discuss the findings obtained from animal and human research providing some support for OP-induced cognitive impairment and neurodegenerative disorders.