**7. Conclusion**

470 Etiology and Pathophysiology of Parkinson's Disease

mutant α-synuclein (Masliah et al., 2000; Lee et al., 2002; Richfield et al., 2002) was found to lead to the develp of granular deposits, but none of these results in the involvment of dopaminergic nerve cellsof the substantia nigra. Previous data demonstrated that truncated α-synuclein (1-120) was aboundantly presents in Lewy bodies extracts (Tofaris et al., 2003). There are two different animal models of Parkinson's disease: the first one is a mouse model that express a truncated human α-synuclein (1-120) under the rat tyrosine hydroxylase promoter on a mouse α-synuclein null background (Tofaris et al., 2006). In this mouse model (TG Syn 120) were found pathological inclusions in substantia nigra and olfactory bulb, a reduction in dopamine levels in the striatum and in spontaneous locomotion and a better response to amphetamine. C-terminally truncated α-synuclein aggregates more quickly than full-lenght protein and has been found in Lewy bodies in human patients. The second one is a rat model (6OH-DA) with the lesion of the ascending nigrostriatal dopamine pathway due to 6-hydroxydopamine injection in the unilateral substantia nigra (Rozas et al., 1997; Picconi et al., 2003). These rats displayed some feautures of parkinsonian pathology. This rat model has been initially used to understand the behavioral functions of the basal ganglia, and to evaluate the brain's ability to compensate for specific neurochemical depletions. Now this model is use has strument to understand the mechanisms of PD pathology and as an experimental basis to develop new antiparkinsonian drugs and treatment strategies, or surgical approaches (Rozas et al., 1997). To deepen the involvement of lysosomal enzyme in Parkinson's disease, a comparative analysis of the activity of βglucocerebrosidase (EC 3.2.1.45), α-mannosidase (EC 3.2.1.24), β-mannosidase (EC 3.2.1.25), β-hexosaminidase (EC 3.2.1.52) and β-galactosidase (EC 3.2.1.23) have been performed in

In particular lysosomal enzymatic activities were determined in cerebellum, cortex and brain-stem. The obtained results show a different expression in these sections of central nervous system of TG Syn 120 mouse model compared to control mice, with a decreased activity of all the enzymes in brain-stem, and an increased activity in the cerebellum. In the

> Alphamannosidase

brain-stem Wistar 20.37±4.33 0.45±0.17 0.32±0.08 3.70±1.22 0.15±0.1

cerebellum Wistar 16.43±3.42 0.51±0.23 0.36±0.13 3.88±0.83 0.1±0.04

striatal Wistar 18.81±3.64 0.3±0.05 0.39±0.29 1.30±0.83 0.1±0.04

A more pronunced differences in lysosomal enzyme expressions were observed in 6OH-DA rats (table 2). A clear reduction of enzyme activities were found in brain-stem, cerebellum

Table 2. Lysosomal enzyme specific activities (μmol min-1/mg total protein x 1000) in, cerebellum, cortico-striatal and brain-stem of control and 6OH-DA rats. Mean ± SD are

6OH-DA 17.61±5.75 0.31±0.1 0.23±0.1 2.82±0.91 0.15±0.08

6OH-DA 11.27\*±2.5 0.25\*±0.05 0.22\*±0.05 2.64\*±0.81 0.08±0.02

6OH-DA 12.85\*±0.92 0.167\*±0.03 0.11\*±0.03 0.48±0.38 0.05\*±0.022

Betamannosidase

Betagalactosidase

Betaglucosidase

different brain sections of the two animal's model.

cortex all the enzymatic activities remain invariated.

Betahexosaminidase

cortico-

given. \*p<0.05 versus control.

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**22** 

Ruiping Xia

*USA* 

**Physiological and Biomechanical Analyses of** 

Parkinson's disease is one of the most common movement disorders characterized by bradykinesia, rigidity, resting tremor and postural instability (Fahn, 2003). It affects nearly five million elderly people worldwide (de Lau & Breteler, 2006). As the population ages, the incidence and prevalence of Parkinson's disease are expected to increase dramatically (Dorsey et al., 2007; Tanner & Goldman, 1996; Tanner & Ben-Shlomo, 1999). Rigidity is one of the clinical hallmark symptoms that characterize and define Parkinson's disease. Rigidity is one form of the increased muscle tone, which is defined as a resistance to a passive movement. Rigidity is clinically characterized by an increase in muscle tone, and is felt as a constant and uniform resistance to the passive movement of a limb persisting throughout its range (Bantam, 2000; Fung & Thompson, 2002; Hallett, 2003). There are two types of rigidity: plastic or lead-pipe rigidity, in which resistance remains uniform, constant and smooth, such as experienced when bending a piece of lead; and cogwheel rigidity, in which tremor is superimposed on increased tone, giving rise to the perception of intermittent fluctuation in muscle tone. The latter is principally attributable to the combination of plastic rigidity and

In addition to being a key element of parkinsonian rigidity, increased muscle tone also characterizes spasticity which is a common motor symptom in a few other neurological disorders, such as multiple sclerosis, stroke and cerebral palsy. Spasticity is clinically described as an increased resistance to passive movement due to hyperexcitability of stretch reflex (Lance, 1980; Rymer & Katz, 1994). Rigidity and spasticity share the characteristic feature of the increased muscle tone to a passive movement. However, the unique lead-pipe resistance can distinguish the increased muscle tone in rigidity from that associated with spasticity. In particular, the differentiation between rigidity and spasticity is not

Rigidity generally responds well to dopaminergic medication and surgical intervention. Thus, it is used as a diagnostic criterion and to evaluate the efficacy of therapeutic interventions (Prochazka et al., 1997). Clinical examination and assessment of rigidity is determined by an examiner's perception of resistance while rotating the limb at major joints, based upon the Unified Parkinson Disease Rating Scale (Fahn & Elton, 1987; Goetz et al., 2008). A better understanding of the physiological and biomechanical characteristics of rigidity merits scientific significance and clinical implication. In this chapter, studies on

straightforward in a clinical scenario (Fung & Thompson, 2002).

**1. Introduction** 

tremor.

*Department of Physical Therapy, Creighton University, Omaha, Nebraska* 

**Rigidity in Parkinson's Disease** 

