Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease ? effect of L-Dopa

Abstract

There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).

Striatal Alterations of Secretogranin-1, Somatostatin, Prodynorphin, and Cholecystokinin Peptides in an Experimental Mouse Model of Parkinson Disease

“…Our present results are in line with the significant increase of somatostatin-like immunoreactivity levels investigated in cerebrospinal fluid (CSF) from 23 patients with untreated early parkinsonian syndrome compared with control subjects (58). However, the opposite was found in CSF of patients with moderate or severe disease (59). Given our data, it may be possible that the increase in somatostatin is a compensatory mechanism trying to restore the DA levels.…”

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

“…Indeed, many classical studies have shown variable degrees of decrease in the CSF HVA levels of PD patients compared with controls (Bernheimer et al, 1966; Guldberg et al, 1967; Johansson and Roos, 1967; Olsson and Roos, 1968; Gottfries et al, 1969; Curzon et al, 1970; van Woert and Bowers, 1970; Godwin-Austen et al, 1971; Mones et al, 1972; Papeschi et al, 1972; Pullar et al, 1972; Cox et al, 1973; Voto Bernales et al, 1973; Weiner and Klawans, 1973; Granerus et al, 1974; Davidson et al, 1977; Tabaddor et al, 1978; Lovenberg et al, 1979; Cunha et al, 1983; Mann et al, 1983; Cramer et al, 1984; Mena et al, 1984; Pezzoli et al, 1984; Burns et al, 1985; Gibson et al, 1985; Jolkkonen et al, 1986; Liu, 1989; Hartikainen et al, 1992; Strittmatter and Cramer, 1992; Chia et al, 1993; Mashige et al, 1994; Eldrup et al, 1995; Cheng et al, 1996; Strittmatter et al, 1996; Kanemaru et al, 1998; Goldstein et al, 2008). Engelborghs et al (2003) reported normal CSF DA and HVA, and decreased DOPAC levels.…”

“…Although levodopa treatment usually increases CSF HVA levels according to the majority of studies, this is not related with clinical improvement, with some exceptions (Durso et al, 1989), and pre-treatment CSF HVA levels does not predict levodopa response (Weiner et al, 1969; Chase, 1970; Curzon et al, 1970; Bertler et al, 1971; Casati et al, 1973; Cox et al, 1973; Mones, 1973; Weiner and Klawans, 1973; Granerus et al, 1974; Davidson et al, 1977; Liu, 1989; Nishi et al, 1989; Strittmatter et al, 1996; Antkiewicz-Michaluk et al, 1997; Durso et al, 1997; Krygowska-Wajs et al, 1997), except in one study which described an association between relatively high pre-treatment CSF HVA levels and a better response to levodopa (Gumpert et al, 1973). One study failed to show changes in ventricular CSF HVA levels after a single acute administration of levodopa (Moussa et al, 1992).…”

“…Several studies have shown reduced CSF levels of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, in PD patients (Guldberg et al, 1967; Johansson and Roos, 1967, 1971; Olsson and Roos, 1968; Gottfries et al, 1969; Chase, 1970; Rinne and Sonninen, 1972; Rinne et al, 1973; Davidson et al, 1977; Mayeux et al, 1984, 1986, 1988; Kostić et al, 1987; Tohgi et al, 1993c, 1997; Mashige et al, 1994; Strittmatter et al, 1996; Engelborghs et al, 2003). Other authors report normal CSF 5-HIAA levels (Papeschi et al, 1970, 1972; Godwin-Austen et al, 1971; Granerus et al, 1974; Davidson et al, 1977; Tabaddor et al, 1978; Cramer et al, 1984; Burns et al, 1985; Chia et al, 1993; González-Quevedo et al, 1993; Volicer et al, 1985; Fukuda et al, 1989).…”

Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

“…In patients with PD, a reduced brain level of somatostatin (SOM) is frequently observed (3)(4)(5)(6)(7). In old Wistar rats, an inhibition of brain SOM receptors can produce catalepsy (8), an animal model of parkinsonian bradykinesia and rigidity.…”