Nicotinic Receptors In Hippocampus Research Articles

Neonatal exposure to the brominated flame-retardant, 2,2′,4,4′,5-pentabromodiphenyl ether, decreases cholinergic nicotinic receptors in hippocampus and affects spontaneous behaviour in the adult mouse

Polybrominated diphenyl ethers (PBDEs) are used as flame-retardants and have recently been shown to increase in the environment and in human milk. We have recently reported that neonatal exposure to 2,2′,4,4′,5-pentaBDE (PBDE 99) can induce persistent aberrations in spontaneous behaviour and also affect learning and memory functions in the adult animal. The present study indicates that the cholinergic system, in its developing stage, can be a target for PBDEs. Neonatal oral exposure of male NMRI mice, on postnatal day 10, to 2,2′,4,4′,5-pentaBDE (12 mg/kg body weight) was shown to decrease the density of cholinergic nicotinic receptors in hippocampus, at an adult age. These findings show similarities to observations made from neonatal exposure to 2,2′,4,4′,5,5′-hexaBDE, PCBs and nicotine, compounds shown to affect cholinergic nicotinic receptors. The animals of the present study also showed disrupted spontaneous behaviour, and the highest dose that did not cause any significant behavioural disruption was 0.4 mg 2,2′,4,4′,5-pentaBDE/kg b.w.

Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice

Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Flame retardants are used to suppress or inhibit combustion processes in an effort to reduce the risk of fire. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), are present and increasing in the environment and in human milk. The present study shows that neonatal exposure to 2,2′,4,4′,5,5′-hexaBDE (PBDE 153), a PBDE persistent both in environment and in human milk, can induce developmental neurotoxic effects, such as changes in spontaneous behaviour (hyperactivity), impairments in learning and memory, and reduced amounts of nicotinic receptors, effects that get worse with age. Neonatal NMRI male mice were orally exposed on day 10 to 0.45, 0.9, or 9.0 mg of PBDE 153/kg of body weight. Spontaneous behaviour (locomotion, rearing, and total activity) was observed in 2−, 4−, and 6-month-old mice, Morris water maze at an age of 6 months. The behaviour tests showed that the effects were dose-response and time-response related. Animals showing defects in learning and memory also showed significantly reduced amounts of nicotinic receptors in hippocampus, using α-bungarotoxin binding assay. The observed developmental neurotoxic effects seen for PBDE 153 are similar to those seen for PBDE 99 and for certain PCBs. Furthermore, PBDEs appear to as potent as the PCBs.

Chronic inhibition of alpha4beta2 nicotinic receptors in the ventral hippocampus of rats: impacts on memory and nicotine response.

Acute and chronic systemic nicotine administration has been shown to cause significant spatial memory improvement. The critical nicotinic receptor subtypes for this effect and their location are still being determined. Nicotinic receptors in the ventral hippocampus have been found to be critically involved in memory. Acute ventral hippocampal infusions of dihydro-beta-erythroidine (DHbetaE), an alpha4beta2 nicotinic receptor antagonist, impaired spatial memory of rats in the radial-arm maze. The current study used chronic ventral hippocampal infusion of DHbetaE as a model of nicotinic receptor loss such as that which occurs in Alzheimer's disease. The therapeutic effect of systemic nicotine treatment in reversing the DHbetaE-induced memory impairment was determined. Rats were pretrained to asymptotic levels of performance on the eight-arm radial maze. Then, they were implanted with bilateral infusion cannulae in the ventral hippocampus, through which 0, 33.3, or 100 microg/side/day of DHbetaE was continuously infused for 4 weeks. The rats were retested on the eight-arm maze throughout infusion period and after withdrawal, and the interaction of acute systemic nicotine injections on memory was tested. The higher (100 microg/side/day) but not the lower (33.3 microg/side/day) DHbetaE dose caused a significant spatial memory impairment. Acute systemic nicotine injections (0, 0.1, 0.2, and 0.4 mg/kg, subcutaneous) attenuated the memory impairing effects of 100 microg/side/day of DHbetaE. There was no significant effect on response latency with the chronic DHbetaE infusion. Acute systemic nicotine infusions did significantly speed responding, an effect which was reversed by chronic hippocampal infusions of DHbetaE. After withdrawal there were no significant lasting effects on choice accuracy or response latency. Wet-dog shakes were significantly elevated during chronic hippocampal DHbetaE administration with no effect during the withdrawal period. These results indicate that chronic inhibition of a subset of nicotinic receptors in the hippocampus results in a significant impairment in the spatial memory choice accuracy. The ability of nicotine to attenuate the impairment supports the development of nicotinic agonist therapy of syndromes, such as Alzheimer's disease, that involve a chronic decrease in the activity of the alpha4beta2 nicotinic receptors and memory impairment.