Persistent neurobehavioral and neurochemical anomalies in middle-aged rats after maternal diazinon exposure.

Hawkey, Andrew B

Pippen, Erica

Kenou, Bruny

Holloway, Zade

Slotkin, Theodore A

Seidler, Frederic J

Levin, Edward D

2023-12-06T14:22:57Z

2023-12-06T14:22:57Z

2022-04

2023-12-06T14:22:57Z

Diazinon is an organophosphate pesticide that has a history of wide use. Developmental exposures to organophosphates lead to neurobehavioral changes that emerge early in life and can persist into adulthood. However, preclinical studies have generally evaluated changes through young adulthood, whereas the persistence or progression of deficits into middle age remain poorly understood. The current study evaluated the effects of maternal diazinon exposure on behavior and neurochemistry in middle age, at 1 year postpartum, comparing the results to our previous studies of outcomes at adolescence and in young adulthood (4 months of age) (Hawkey 2020). Female rats received 0, 0.5 or 1.0 mg/kg/day of diazinon via osmotic minipump throughout gestation and into the postpartum period. The offspring were tested on a battery of locomotor, affective, and cognitive tests at young adulthood and during middle age. Some of the neurobehavioral consequences of developmental DZN seen during adolescence and young adulthood faded with continued aging, whereas other neurobehavioral effects emerged with aging. At middle age, the rats showed few locomotor effects, in contrast to the locomotor hyperactivity that had been observed in adolescence. Notably, though, DZN exposure during development impaired reference memory performance in middle-aged males, an effect that had not been seen in the younger animals. Likewise, middle-aged females exposed to DZN showed deficient attentional accuracy, an effect not seen in young adults. Across adulthood, the continued potential for behavioral defects was associated with altered dopaminergic function, characterized by enhanced dopamine utilization that was regionally-selective (striatum but not frontal/parietal cortex). This study shows that the neurobehavioral impairments from maternal low dose exposure to diazinon not only persist, but may continue to evolve as animals enter middle age.

S0300-483X(22)00101-9

0300-483X

1879-3185

https://hdl.handle.net/10161/29478

eng

Elsevier BV

Toxicology

10.1016/j.tox.2022.153189

Animals

Rats

Organophosphorus Compounds

Diazinon

Insecticides

Behavior, Animal

Female

Male

Organophosphates

Persistent neurobehavioral and neurochemical anomalies in middle-aged rats after maternal diazinon exposure.

Journal article

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

153189

Duke

Nicholas School of the Environment

School of Medicine

Trinity College of Arts & Sciences

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Neurobiology

Pharmacology & Cancer Biology

Psychiatry & Behavioral Sciences

Duke Cancer Institute

Psychology & Neuroscience

Environmental Sciences and Policy

Institutes and Provost's Academic Units

University Institutes and Centers

Duke Institute for Brain Sciences

Initiatives

Duke Science & Society

Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

Published

472