oxytocin and Parkinson-Disease

Increased oscillatory activity has been demonstrated in the basal ganglia of Parkinson's disease (PD) patients. The aim of the present study was to evaluate the effects of oxytocin on local field potentials (LFPs) in a rotenone-induced rat model of PD. Adult male Sprague-Dawley rats were unilaterally injected with rotenone (3 µg/µl in DMSO) into the left substantia nigra pars compacta whereas vehicle group was received only DMSO. PD developed rats were then administered either oxytocin (160 µg/kg/day, i.p.) or saline for three weeks. Following treatment period, LFPs were recorded from the left striatum of freely moving rats and neuronal cell loss was evaluated by Nissl staining. We found significant increase in all frequency bands except delta in saline group when compared with vehicle (p < 0.0005), while treatment of oxytocin prevented these alterations in EEG recordings. Besides, histopathological evaluation of the striatal sections revealed a significant cell loss (p < 0.005), whereas administration of rats with oxytocin significantly lessened the neuronal death. These findings suggest that injury of dopaminergic neurons triggers exaggerated neuronal oscillations in the striatum and oxytocin may have some inhibitory effects on neuronal activity in PD.

Topics: Animals; Apomorphine; Behavior, Animal; Disease Models, Animal; Electroencephalography; Electrophysiological Phenomena; Male; Neostriatum; Neurons; Oxytocin; Parkinson Disease; Rats; Rats, Sprague-Dawley; Rotation

Oxytocin (OT) is essentially associated with uterine contraction during parturition and milk ejection reflex. Although several studies implicate the role of OT in anti-inflammatory, anti-oxidative and anti-apoptotic pathways, there is a lack of data with regard to the protective effects of oxytocin in neurodegenerative models such as Parkinson's disease (PD). The present study was undertaken to investigate the neuroprotective effects of oxytocin (OT) on rotenone-induced PD in rats. Twenty adult Sprague-Dawley rats were injected with rotenone (3 μg/μl in DMSO) or vehicle (1 μl DMSO) into the left substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) under stereotaxic surgery, and PD model was assessed by rotational test ten days after drug infusion. The valid PD rats were randomly divided into two groups; Group 1 (n=7) and Group 2 (n=7) were administered saline (1 ml/kg/day, i.p.) and oxytocin (160 μg/kg/day, i.p.) through 20 days, respectively. The effects of OT treatment were evaluated by behavioral, histological and immunohistochemical parameters. Apomorphine-induced stereotypic rotations in PD rats were significantly inhibited by OT treatment (p<0.05). In addition, immunohistochemical studies clearly demonstrated the suppression of Bax, caspase-3, caspase-8 and elevation of Bcl-2 and tyrosine hydroxylase immunoexpression in OT-treated rats compared to saline group. Our findings suggest that oxytocin may have cytoprotective and restorative effects on dopaminergic neurons against rotenone-induced injury. The underlying mechanism may be associated with the inhibition of apoptotic pathways.

Topics: Animals; Apomorphine; Behavior, Animal; Body Weight; Cell Death; Dopaminergic Neurons; Male; Neostriatum; Oxytocin; Parkinson Disease; Rats; Rats, Sprague-Dawley; Rotenone

We determined the number of immunocytochemically identified oxytocin (OXT) and vasopressin (AVP) neurons in the paraventricular nucleus (PVN) of the human hypothalamus of six Parkinson's disease (PD) patients ranging from 59 to 83 years of age. Six subjects without a primary neurologic or psychiatric disease, ranging from 69 to 88 years of age, served as controls. The OXT-immunoreactive cell number in the PVN of the PD patients was 22% lower than that of the control subjects. Although Lewy bodies were present in the nucleus basalis of Meynert, there were no Lewy bodies in the PVN of these patients. Doubt is raised about the presumed direct relationship between the presence of Lewy bodies and neuronal degeneration in PD. The AVP-immunoreactive cell number in the PD patients showed a similar decreasing trend, but the 18% reduction failed to reach statistical significance. The presence of tyrosine hydroxylase-positive neurons in the PVN was not affected in PD patients, supporting the notion that dopaminergic neurons of the mesencephalon, but not of the hypothalamus, are affected in PD. The decreased number of OXT-containing neurons in the PVN suggests that dopamine may be important for the function of these neurons and may provide a neural basis for some autonomic and endocrine disturbances in PD.

Topics: Aged; Aged, 80 and over; Arginine Vasopressin; Female; Humans; Immunohistochemistry; Lewy Bodies; Male; Middle Aged; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Parkinson Disease; Substantia Innominata; Tyrosine 3-Monooxygenase

Topics: Administration, Oral; Animals; Antidepressive Agents; Antiparkinson Agents; Chemical Phenomena; Chemistry; Depression; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Injections, Intravenous; Melanocyte-Stimulating Hormones; Oxytocin; Parkinson Disease; Peptides; Rabbits; Rats; Thyrotropin-Releasing Hormone