Publications (16) View all
-
Article: Blockade of mGluR5 reverses abnormal firing of subthalamic nucleus neurons in 6-hydroxydopamine partially lesioned rats.
[show abstract] [hide abstract]
ABSTRACT: Activation of metabotropic glutamate receptor 5 (mGluRs) in the subthalamic nucleus (STN) results in burst-firing activity of STN neurons, which is similar to that observed in Parkinson's disease (PD). We examined the effects of chronic and systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, in firing activity of STN neurons in partially lesioned rats by 6-hydroxydopamine (6-OHDA). In 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (4 microg) into the medial forebrain bundle produced a partial lesion causing 36% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc). The 6-OHDA lesion in vehicle-treated rats showed an increasing firing rate and a more irregular firing pattern of STN neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, 14 days) produced neuroprotecive effects on the TH-ir neurons and normalized the hyperactive firing activity of STN neurons in 6-OHDA partially lesioned rats. These data demonstrate that partial lesion of the nigrostriatal pathway increases firing activity of STN neurons in the rat, and chronic, systemic MPEP treatment has the neuroprotective effect and reverses the abnormal firing activity of STN neurons, suggesting that MPEP has an important implication for the treatment of PD.The Chinese journal of physiology 10/2011; 54(5):303-9. · 0.56 Impact Factor -
Article: Alterations of emotion, cognition and firing activity of the basolateral nucleus of the amygdala after partial bilateral lesions of the nigrostriatal pathway in rats.
[show abstract] [hide abstract]
ABSTRACT: Although increasing evidence indicates that psychiatric symptoms are crucial characteristic of the early stage of Parkinson's disease (PD) and precede motor impairments, the neuronal firing activity of the basolateral nucleus of the amygdala (BLA) in the psychiatric symptom of PD and the involved mechanism are still unclear. In the present study, we examined the changes in emotional and cognitive tests not focused on motor fluency and firing activity of projection neurons in the BLA rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum, and the effects of apomorphine and the medial prefrontal cortex (mPFC) on these changes. Injection of 6-OHDA (10.5 μg) into the dorsal striatum produced 18-22% and 26-30% loss of tyrosine hydroxylase immunoreactive neurons in the ventral tegmental area and substantia nigra pars compacta of rats, respectively. The striatal lesions induced anxiety-like responses in the rats but did not result in depressive-like behavior or cognitive impairments. In the lesioned rats, the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and the firing pattern of BLA projection neurons was not changed. No significant differences were observed either in behaviors or firing activity of BLA projection neurons by further ibotenic acid lesions of the mPFC in the lesioned rats. Systemic administration of cumulative apomorphine (10-160 μg/kg) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA-lesioned and combined 6-OHDA- and mPFC-lesioned rats, but the latter needed more apomorphine stimulation. These data suggest that the anxiety in early stage of PD is possibly related to the decrease in firing activity of BLA projection neurons, which may be regulated by the activation of dopamine receptor in the mPFC.Brain research bulletin 05/2011; 85(6):329-38. · 2.18 Impact Factor -
Article: Effects of chronic, systemic treatment with the dopamine receptor agonist R-apomorphine in partially lesioned rat model of Parkinson's disease: an electrophysiological study of substantia nigra dopamine neurons.
[show abstract] [hide abstract]
ABSTRACT: Previous studies have suggested that R-apomorphine (R-APO), a non-selective dopamine (DA) receptor agonist, has neuroprotective effects in the experimental models of Parkinson's disease (PD). In this study, we investigated the effects of chronic, systemic treatment with R-APO in the firing activity of substantia nigra pars compacta (SNc) DA neurons in 6-hydroxydopamine (6-OHDA) partially lesioned rats. In the 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (20.1 microg) into the striatum produced a partial lesion causing 41% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the SNc. In the partially lesioned rats, chronic, systemic treatment of R-APO (10 mg/kg/day, s.c., 11 days) attenuated loss of TH-ir neurons in the SNc. The partial lesion of the nigrostriatal pathway and R-APO treatment did not change the firing rate and firing pattern of DA neurons in the SNc of rats. In contrast, the R-APO treatment increased the number of spontaneously active DA neurons of the SNc in the partially lesioned rats, while the lesion decreased the number of spontaneously active DA neurons. In addition, the chronic R-APO treatment decreased the responsiveness of the DA neurons to intravenously administrated R-APO in the partially lesioned rats. These results indicate that chronic, systemic R-APO treatment has the neuroprotective effect, and reverses the decrease in the number of spontaneously active DA neurons in the SNc whereas the treatment induces a reduction in the sensitivity of DA receptors in the SNc to R-APO stimulation in this model.The Chinese journal of physiology 04/2011; 54(2):96-104. · 0.56 Impact Factor -
Article: Chronic, systemic treatment with a metabotropic glutamate receptor 5 antagonist produces anxiolytic-like effects and reverses abnormal firing activity of projection neurons in the basolateral nucleus of the amygdala in rats with bilateral 6-OHDA lesions.
[show abstract] [hide abstract]
ABSTRACT: Although 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective metabotropic glutamate receptor 5 antagonist, improves the motor symptoms of Parkinson's disease (PD), the effects of MPEP on the psychiatric symptom of PD and the mechanism involved are still unclear. In the present study, we examined the effects of MPEP in anxiolytic-like behavior and firing activity of projection neurons in the basolateral nucleus of the amygdala (BLA) in rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum. Rats were divided into three groups, sham-operated group, 6-OHDA lesion with vehicle treatment group and 6-OHDA lesion with MPEP treatment group. Injection of 6-OHDA (10.5 μg) into the dorsal striatum produced 31.5% loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the SNpc. The 6-OHDA-lesioned rats showed anxiety behavior and the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and no difference was found in the firing pattern of these neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, i.p.; 14 days) attenuated loss of TH-ir neurons, produced anxiolytic-like effect and normalized the abnormal firing rate of projection neurons of the BLA in rats with the bilateral lesions. Systemic administration of cumulative apomorphine (10-160 μg/kg, i.v.) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA lesion with vehicle-treated and MPEP-treated rats, but the 6-OHDA lesion decreased the response of BLA projection neurons to apomorphine stimulation, while MPEP reversed the reactivity of these neurons. These data demonstrate that the partial lesion of the nigrostriatal pathway causes anxiety symptom and decreases firing rate of BLA projection neurons in the rat. Furthermore, chronic, systemic MPEP treatment has the neuroprotective and anxiolytic-like effects, and reverses the abnormal firing rate of BLA projection neurons, suggesting that MPEP has important implication for the treatment of PD.Brain research bulletin 02/2011; 84(3):215-23. · 2.18 Impact Factor -
Article: The pyramidal neurons in the medial prefrontal cortex show decreased response to 5-hydroxytryptamine-3 receptor stimulation in a rodent model of Parkinson's disease.
[show abstract] [hide abstract]
ABSTRACT: In the present study, effect of SR 57227A, a selective 5-hydroxytryptamine-3 (5-HT(3)) receptor agonist, on the firing activity of pyramidal neurons in the medial prefrontal cortex (mPFC) was studied in normal rats and rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta by using extracellular recording. Systemic administration of SR 57227A (40-640 μg/kg, i.v.) decreased the mean firing rate of pyramidal neurons in normal and the lesioned rats. This inhibition was significant only at doses higher than 320 μg/kg and 640 μg/kg in normal and the lesioned rats, respectively, and was reversed by i.v. administration of 5-HT(3) receptor antagonist tropisetron or GABA(A) receptor antagonist bicuculline. Furthermore, local application of SR 57227A (0.01 μg) in the mPFC inhibited the firing rate of pyramidal neurons in normal rats while having no effect on firing rate in the lesioned rats. The i.v. administration of bicuculline excited the pyramidal neurons in normal rats, and then local application of SR 57227A did not alter the mean firing rate of these neurons. However, these two drugs did not affect the activity of the pyramidal neurons in the lesioned rats. We conclude that activation of 5-HT(3) receptors inhibited pyramidal neurons in the mPFC of normal rats via GABAergic interneurons, and degeneration of the nigrostriatal pathway decreased response of the pyramidal neurons to SR 57227A, suggesting the dysfunction of 5-HT(3) receptors and/or down-regulation of the expression on GABAergic interneurons in the lesioned rats.Brain research 02/2011; 1384:69-79. · 2.46 Impact Factor
