Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Abstract

a b s t r a c tPesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 g/L and it was completely eliminated after 96 h.

Effects of exposure to pyrethroid cyfluthrin on serotonin and dopamine levels in brain regions of male rats

“…Pyrethroids, highly lipophilic compounds, readily cross the blood-brain-barrier (Anadón et al, 1996; and they can reach the CNS at concentrations that can be potentially neurotoxic, especially when the exposure to these chemical agents occurs in early life when the brain is in a highly active neurodevelopmental phase as the synaptogenesis (Nasuti et al, 2013). Also after a long-term exposure to moderate dose, pyrethroids could induce neurological complications (Singh et al, 2012a(Singh et al, , 2012b.…”

Evidence for a Dopamine Intrinsic Direct Role in the Regulation of the Ovary Reproductive Function: In Vitro Study on Rabbit Corpora Lutea

“…A previously reported high performance liquid chromatography (HPLC) method with electrochemical amperometric detection (EC) was utilized to measure DA concentration in CL [21]. Tissues from each animal were individually homogenized for 2 min with a Dyna-Mix homogenizer (Fisher Scientific) in 500 µL of 0.05 N perchloric acid solution containing (w/v) 0.064% 1-octanesulphonic acid sodium salt, 0.060% heptanesulphonic acid sodium salt, 0.004% sodium EDTA, 0.010% sodium metabisulphite and 25 ng/ml DHBA as an internal standard.…”

Developmental neurotoxicity of succeeding generations of insecticides

“…Similarly, postnatal exposure increases blood-brain barrier permeability (Sinha and others 2004), causes oxidative stress (Gupta and others 1999b; Nasuti and others 2007; Sinha and others 2006) and impairs the cholinergic muscarinic, dopaminergic and noradrenergic systems (Ahlbom and others 1994; Carloni and others 2012; Carloni and others 2013; Eriksson and Nordberg 1990; Nasuti and others 2013; Nasuti and others 2007). However, several other effects were also identified.…”

“…These include unbalance between pro- and anti-inflammatory responses and impairment of the serotonergic system, decreased nitric oxide, glutamate and calcium in several brain regions even several months after the end of exposure (Carloni and others 2012; Carloni and others 2013; Nasuti and others 2013). As for behavioral effects, both locomotor activity and rearing are increased in response to early postnatal exposure (Ahlbom and others 1994; Nasuti and others 2007; Talts and others 1998), whereas spatial working memory (Carloni and others 2012; Carloni and others 2013; Nasuti and others 2013), and conditioned avoidance responses are decreased (Sinha and others 2006). Behavioral effects are identified even long after the end of exposure, in adult and aged rats, which suggests that early life exposure to type I PIs interferes with brain-aging processes.…”