Nigral injection of antisense oligonucleotides to synaptotagmin I using HVJ-liposome vectors causes disruption of dopamine release in the striatum and impaired skill learning.
ABSTRACT To produce an animal model of a dopa-responsive motor disorder with depletion of dopamine (DA) release in the striatum by dysfunction of the transmitter release machinery of the nigrostriatal DA system, we performed an intra-nigral injection of an HVJ-liposome gene transfer vector containing antisense oligodeoxynucleotides (ODNs) against synaptotagmin I (SytI), a key regulator of Ca(2+)-dependent exocytosis and endocytosis in adult rats. A unilateral intra-nigral injection of HVJ-liposome vectors containing antisense ODNs against SytI (syt-AS) caused a moderate disruption of methamphetamine-induced release of DA in the treated side of the striatum, while the syt-AS treatment did not affect physiological release of DA in the treated striatum. A bilateral intra-nigral injection of HVJ-liposome vectors containing syt-AS induced an impairment of the striatal DA-mediated acquisition of skilled behavior in a rotarod task without any deficits in general motor functions, such as spontaneous locomotor activity, motor adjusting steps, equilibrium function, or muscle strength. These findings suggest that an intra-nigral treatment with HVJ-liposome vectors containing syt-AS may cause a long-lasting nigral knockdown of SytI which, in turn, leads to a moderate dysfunction of the DA release machinery in the terminals of the nigrostriatal DA system and a subsequent mild depletion of DA release in the striatum.
- SourceAvailable from: Heinz SteinerHandbook of Behavioral Neuroscience 01/2010; 20:501-525.
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ABSTRACT: Since the mass production of plastics began in the 1940s, microplastic contamination of the marine environment has been a growing problem. Here, a review of the literature has been conducted with the following objectives: (1) to summarise the properties, nomenclature and sources of microplastics; (2) to discuss the routes by which microplastics enter the marine environment; (3) to evaluate the methods by which microplastics are detected in the marine environment; (4) to assess spatial and temporal trends of microplastic abundance; and (5) to discuss the environmental impact of microplastics. Microplastics are both abundant and widespread within the marine environment, found in their highest concentrations along coastlines and within mid-ocean gyres. Ingestion of microplastics has been demonstrated in a range of marine organisms, a process which may facilitate the transfer of chemical additives or hydrophobic waterborne pollutants to biota. We conclude by highlighting key future research areas for scientists and policymakers.Marine pollution bulletin 12/2011; 62(12):2588-97. · 2.63 Impact Factor
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ABSTRACT: The rotarod test is widely used to evaluate the motor coordination of rodents, and is especially sensitive in detecting cerebellar dysfunction. However, mice with striatal dopamine depletion show only mild or no motor deficit on the typical accelerating rotarod. This suggests that dopamine-depleted mice are useful as animal models for non-motor symptoms, because the influence of motor deficit is minimum and easy to discriminate from cognitive aspects of the behavioral change. The typical accelerating rotarod test is designed to evaluate maximal motor performance and is not optimized to detect motor skill learning. In an attempt to make the test more selective to motor skill learning rather than maximal gait performance, we modified the rotarod test by using a slowly rotating large drum to obtain a steep learning curve. Furthermore, administration of nomifensine, a dopamine uptake inhibitor, improved the learning. On the other hand, apomorphine, an agonist of dopamine autoreceptor, a dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impaired the learning. These pharmacological profiles fit the involvement of the so-called phasic dopamine neurotransmission. Using our modified procedure, we found impaired learning of Parkin-deficit mice, which has not been detected in typical accelerating rotarod. The modified rotarod test would be useful for evaluation of dopamine involvement in the acquisition of motor skill learning.Journal of neuroscience methods 03/2010; 189(2):180-5. · 2.30 Impact Factor