Increased DAT and VMAT2 levels were accompanied by alterations of mRNA levels of nuclear transcription factors that control dopamine neuron development and regulate DAT and VMAT2 levels in adulthood. At 12 weeks of age, control and heptachlor-exposed offspring were administered a moderate dose (2x 10 mg/kg) of the parkinsonism-inducing agent MPTP. Greater neurotoxicity as evidenced by a greater loss of striatal dopamine and potentiation of increased levels of glial fibrillary acidic protein and a-synuclein was observed GW4869 in heptachlor-exposed offspring.

The neurotoxicity observed was greater in the male offspring than the female offspring, suggesting that males are more Susceptible to the long-term effects of developmental heptachlor exposure, These data

suggest that developmental heptachlor exposure causes long-term alterations of the dopamine system thereby rendering it more susceptible to dopaminergic damage in adulthood. (C) 2008 Elsevier Inc. All rights reserved.”
“We have previously reported that a single injection of endotoxin, lipopolysaccharide (LPS, 5 mg/kg, i.p.), causes a delayed and progressive loss of TH-IR neurons in the substantia nigra (SN) in C57BL/six male mice. In this study, we determined sex differences and behavioral deficits accompanying the loss of TH-IR neurons in response to peripheral LPS injection. A single injection of LPS (5 mg/kg, i.p.) failed to produce any loss of TH-IR neurons in the SN of female mice over a 12-month period. To determine if multiple-injections were required, LXH254 price female mice received five injections of LPS (5 mg/kg, i.p.) at either weekly or monthly intervals. Behavioral motor

ability and TH-IR neuronal loss were determined after the first injection of LPS. We found significant differences in both behavioral activities and neuronal loss between these two injection paradigms. Between 7 and until 20 months after the first injection of LPS, progressive behavioral changes, measured by rotor-rod and open-field activities, and neuronal loss in SN were observed in monthly injected, but not in weekly injected mice. In addition, reduced rotor-rod ability in monthly injected mice were restored following treatment of L-dopa/carbidopa (30 mg/3 mg/kg), i.p.). Approximately 40 and 50% loss of TH-IR neurons at 9 and 20 months, respectively, was observed after exposure to LPS, suggesting that the behavioral deficit is related to loss of dopamine function in the nigra-striatal pathway. More intense immuno-staining of alpha-synuclein and inflammatory markets were detected in brain sections exposed to LPS. In conclusion, these results show that multi-LPS monthly injections can induce a delayed and progressive loss of TH-IR neurons and motor deficits which resemble the progressive nature of Parkinson’s disease. Further, the present study reveals a clear sex difference: female mice are more resistant to LPS than male mice.