6-OHDA model

In the unilateral 6-OHDA model, also known as the hemiparkinson model, the intact hemisphere serves as an internal control structure (Perese et al., 1989 Schwarting and Huston, 1996). Among the motor tests used following 6-OHDA... 

In summary, the 6-OHDA model does not mimic all pathological and clinical features of human Parkinsonism. It induces DA neuron death, whereas the formation of cytoplasmatic inclusions (LB) does not occur. However, these models are very useful for testing cell replacement therapies or neuroprotective treatments. 

Lerrdviral vectors as a gerre delivery system irr dre mouse midbrahr Cellular arrd behavioral improvemerrts irr a 6-OHDA model of Par khrsorr s disease usirrg GDNF. Exp Neur ol 164- 15—24. 

Lentiviral vectors as a gene dehvery system in the mouse midbrain Cellular and behavioral improvements in a 6-OHDA model of Parkinson s disease using GDNE. Exp Neurol 164 15-24. 

Since PD is caused by a relatively specific degeneration of the DA nigrostriatal tract and as there are specific toxins, for DA neurons, i.e. 6-OHDA and MPTP, it should be possible to produce appropriate experimental models. Certainly both toxins cause rotational behaviour in rats (Fig. 7.7) but no rodent shows a syndrome suggestive of PD. Tremor and akinesia can be seen, however, in primates after such toxins and these are being more widely used in experimental studies of PD and drug evaluation. Reserpine causes a depletion of all brain monoamines and produces motor defects in rats, which, even if not PD-like, do respond to DA manipulation. 

I. den Daas, P. de Boer, P. G. Tepper, H. Rollema, A. S. Horn, Orally Active Carbamate Prodrugs of the Selective Dopamine Agonist N-0437 In-vivo Activities in the 6-OHDA Turning Model and in-vitro Activities , J. Pharm. Pharmacol. 1991, 43, 11 - 16. 

Norepinephrine may also play a role in the induction of immediate early genes in response to pup exposure (Thomas and Palmiter, 1997). Norepinephrine has been linked to maternal behavior in certain other animal models, such as sheep and rats. It may also play a role in olfactory recognition and memory in rats. Intraventricular administration of 6-OHDA prior to birth has been noted to impair postpartum maternal behavior administration after birth had no such effect. 

Guo S, Yan J, Yang T, Yang X, Bezard E, Zhao B. 2007. Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson s disease through inhibition of ROS-NO pathway. Biol Psychiatry 62 1353-1362. 

Yuan H, Sarre S, Ebinger G, Michotte Y. Neuropro-tective and neurotrophic effect of apomorphine in the striatal 6-OHDA-lesion rat model of Parkinson s disease. Brain Res. 2004 1026 95-107. 

The cAMP pathway is thought to play an important role in the gene expression regulated by the dopamine receptors. Indeed, many treatments that induce gene expression in the striatum are also known to increase cAMP levels. In the model of 6-OHDA-lesioned animal, gene induction was triggered by D1 agonist treatments or by l-DOPA via D1... 

Allen SM, Davis WM (1999) Relationship of dopamine to serotonin in the neonatal 6-OHDA rat model of Lesch-Nyhan syndrome. Behav Pharmacol 70 467-474. 

Annett LE, Rogers DC, Dunnett SB (1990b) Unilateral 6-OHDA lesions in marmosets a primate model for neural transplantation in Parkinson s disease. In Franks AJ, Ironside J, Mindham RHS, Smith RJ, Spokes EGS, Winlow W (Eds), Function and Dysfunction in the Basal Ganglia, pp. 181-197. Pergamon, Oxford. 

Carey RJ (1990) Dopamine receptors mediate drug-induced but not Pavlovian conditioned contralateral rotation in the unilateral 6-OHDA animal model. Brain Res 575 292-298. 

Rosenblad C, Kirik D, Bjorklund A (2000) Sequential administration of GDNF into the substantia nigra and striatum promotes dopamine neuron survival and axonal sprouting but not striatal reinnervation or functional recovery in the partial 6-OHDA lesion model. Exp Neurol 767 503-516. 

There are both toxin and genetic animal models of PD. Many different toxins are used to generate DA degeneration. The most frequently used toxins in rodent models of PD are 6-hydroxydopamine (6-OHDA) and 1-methyM-phenyl-l, 2, 3,... 

In PD, animal studies are underw ay with IGL-1. N-ter-minal tripeptide of IGF-1 wa.s peripherally administered to 6-OHDA mouse models of PD and results indicated that administration after the onset of nigrostriatal dopamine depletion improved long term parkinsonian motor deficits however IGF-1 administration did not prevent the loss of tyrosine hydroxylase in the substantia nigra pars compacta or the striatum (Krishnamurthi et al., 2004). Human trials of IGF have not yet been conducted in PD. 

VEGF has also been shovm to promote neuroprotection in the 6-OHDA mouse model of PD by activating the proliferation of glia and by promodng angiogenesis (Yasuhara et al., 2004). Human trials will likely be initiated in the future, once optimal dosing and route of administration have been established. 

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