Neurotoxicology
-
Maternal methamphetamine (MA) abuse during pregnancy has been proved to induce various impacts on the development of infant and child. In this study, we examined whether prenatal exposure to MA would affect the development of nociceptive system by measuring the responses to noxious stimulation in the developing rat. Adult female Sprague-Dawley rats received bi-daily subcutaneous injection of methamphetamine (5mg/kg) or isovolumetric normal saline since the day of mating till the day of delivery. ⋯ The MA group rats had significantly lower tactile withdrawal values in von Frey test and higher pain scores in the late phase of pain in the formalin test than those of the control rats. There is a gender difference of nociceptive hypersensitivity manifested as that the female MA group rats had significantly lower withdrawal thresholds and higher pain scores in response to formalin injection than the male MA group rats. These results suggest that prenatal MA exposure could predispose an alteration in the development of nociceptive neuronal network, which leads to a long-lasting status of hypersensitivity to pain stimulations in the offspring.
-
Gadolinium (Gd), a rare-earth lanthanides metal, is widely utilized for various industrial and medical purposes, particularly in brain magnetic resonance imaging. However, its potential effects on the impairment of the central nervous system remain uncertain, especially with regard to the mitochondria, the potential primary target in metal-induced neural injury. This study investigates the effects of gadolinium on mitochondrial energy metabolism, ROS accumulation, and cell death toward cortical neurons. ⋯ Inhibition of both cytochrome c release and caspase-3 activation could significantly reduce Gd-induced neuron cell death. All these results suggest that gadolinium cause neuron cell apoptosis primarily by inhibiting mitochondrial function and inducing oxidative stress. The present work provides new insight into the toxicological mechanism of gadolinium in neurons.
-
In our environment, mammals (including humans) are exposed to various types of ionizing radiation and both persistent and non-persistent toxic chemicals. It is known that ionizing radiation, as well as methyl mercury, can induce neurotoxicological and neurobehavioural effects in mammals. These developmental neurotoxic effects can be seen following exposure during gestation. ⋯ The animals were then subjected to a spontaneous behaviour test at 2 and 4 months, and a water maze test at the age of 5 months. Neither the single dose of MeHg (0.4 mg/kg bw) nor the radiation dose of 0.2 Gy affected their spontaneous behaviour, whereas the co-exposure to external gamma-radiation and MeHg caused developmental neurotoxic effects. The study shows that gamma-radiation and MeHg can interact and significantly exacerbate developmental neurotoxic effects, as manifested by disrupted spontaneous behaviour, lack of habituation, and impaired learning and memory functions.
-
AICAR (5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside, Acadesine, AICA riboside) is an activator of AMP-activated protein kinase (AMPK). The results of recent studies suggest that AICAR, in addition to its application for treating metabolic disorders, may also have therapeutic potential for treating neuroinflammatory diseases where reactive microglia play an etiological role. However, the molecular mechanisms of action by which AICAR exerts its anti-inflammatory effects still remain unclear or controversial. ⋯ The presented evidence supports the conclusion that AMPK activated by AICAR is involved in regulation of ROS and cytokine production (IL-1 beta, TNF-alpha (6h), IL-10 and TGF-beta) as well as arginase I and PGC-1alpha expression. Furthermore, we found that the effects of AICAR on IL-6 and TNF-alpha (12, 24h) release and on the expression of iNOS and NF-kappaB p65 are not AMPK-dependent because the pre-treatment of LPS-activated microglia with compound C (a pharmacological inhibitor of AMPK) did not reverse the effect of AICAR. The results of the presented study provide additional data about AMPK-dependent and -independent mechanisms whereby AICAR may modulate inflammatory response of microglia.
-
Occupational and environmental exposure to manganese (Mn) is associated with various neurobehavioral and movement dysfunctions. However, few studies have systemically examined the neurochemical effects of Mn exposure. ⋯ The cognitive decline observed in welders exposed to Mn was associated with a decreased mI/tCr ratio in the ACC. The depletion of mI in welders may reflect possible glial cell swelling and/or detoxification processes associated with long-term exposure to Mn.