Substance P receptors are differentially affected in Parkinson's and Alzheimer's disease

Abstract

We have quantified by receptor autoradiography the number of NK1 receptors, using [125I] Bolton-Hunter labeled substance P, in striatum and pallidum (internal (GPi) or external (GPe) segment) of patients suffering from Alzheimer's (AD) and Parkinson's disease (PD). When compared to non-neurologic controls, a significant increase in the number of NK1 sites has been observed in the striatum of PD patients. No significant differences were observed for the GPi and GPe. We observed no significant differences from controls in the number of NK1 sites in the striatum and pallidum of AD cases. However, the number of NK1 sites in the striatum of AD patients was significantly lower than that of PD patients. These results show that the expression of NK1 receptors in the basal ganglia is affected in PD.

Gender and age affect NK1 receptors in the human brain – a positron emission tomography study with [18F]SPA-RQ

“…Recent animal and human studies have suggested potential roles for SP and NK1R in CNS physiology, e.g. in the regulation of mood, anxiety/stress responses, reward, neurogenesis, nausea and vomiting, motor control and pain (De Felipe et al, 1998 ;Hesketh et al, 2003 ;Kramer et al, 1998 ;Morcuende et al, 2003 ;Murtra et al, 2000 ;Rioux and Joyce, 1993 ;Santarelli et al, 2001 ;Stumm et al, 2001). To date, clinical trials have shown only that SP NK1R antagonists (SPAs) such as aprepitant are effective anti-emetics leading to their use in the prevention of chemotherapy-induced nausea and vomiting (Hesketh et al, 2003 ;Navari et al, 1999).…”

Automated radiosynthesis of [18F]SPA‐RQ for imaging human brain NK1 receptors with PET

“…5,7 Recently, [ 18 F]SPA-RQ (3; Figure 1) has been developed for imaging brain NK 1 receptors in vivo with positron emission tomography (PET) and validated for imaging in human subjects in Europe. [8][9][10] However, this radioligand had not been used in human subjects in the USA preceding this work.…”

“…The neurokinin type-1 (NK 1 ) receptor is acted on by substance P, which has been implicated in several neuropsychiatric disorders such as depression, 1,2 schizophrenia, 3,4 Parkinson's disease 5,6 and Alzheimer's disease. 5,7 Recently, [ 18 F]SPA-RQ (3; Figure 1) has been developed for imaging brain NK 1 receptors in vivo with positron emission tomography (PET) and validated for imaging in human subjects in Europe.…”

Neurokinin-1 receptor activation in globus pallidus

“…By acting on neurokinin-1 receptors (substance P receptors), substance P has been demonstrated to modulate neuronal activity in a number of brain regions. Experimental and preclinical evidence suggested that substance P is involved in several neurological diseases, including degeneration of human motoneurons (Vacca-Galloway and Steinberger, 1986; Tang et al, 1990; Yung et al, 1992), depression (Santarelli and Saxe, 2003; Czeh et al, 2005), Alzheimer's disease (Rioux and Joyce, 1993; Rosler et al, 2001), Parkinson's disease (Pezzoli et al, 1984; Rioux and Joyce, 1993) and Huntington's disease (Lastres-Becker et al, 2002). In terms of cellular actions, previous electrophysiological studies have demonstrated that substance P can enhance firing rate and depolarized neurons in several brain areas (Stanfield et al, 1985; Norris et al, 1993; Shirakawa and Moore, 1994; Napier et al, 1995; Minabe et al, 1996; Li and Guyenet, 1997; Wang and Robertson, 1997, 1998; Mitrovic and Napier, 1998; Preston et al, 2000; Bailey et al, 2004).…”

“…Indeed, previous studies have shown that the concentration of substance P in cerebrospinal fluid and the expression of substance P or its receptor in striatum are altered in Parkinson's disease (Pezzoli et al, 1984; Rioux and Joyce, 1993; Betarbet and Greenamyre, 2004). Furthermore, intracerebroventricular administration of substance P increases dopamine content in 6-hydroxydopamine (6-OHDA) lesioned rats (Krasnova et al, 2000), which implicates its potential in the treatment of Parkinson's disease.…”