Training effects of a 12-week walking program on Parkinson disease patients and community-dwelling older adults.

BACKGROUND: Introducing evidence-based exercise guidelines of Parkinson's disease (PD) into clinical practice and community settings has been highlighted. AIM: This study tested the feasibility and compared the weekly effects of a 12-week walking training program on PD patients and community-dwelling seniors. DESIGN: A prospective quasi-experimental design was used. PD patients in Hoehn and Yahr Stage I through III (PG) and community-dwelling adults older than 65 were recruited (CG). METHODS: In the outpatient department of a hospital, the information of personal data, coordination test, and walking ability of participants were collected first. They then participated in a 36-session, 12-week treadmill walking training program. RESULTS: Weekly data of step length and velocity in PG and CG were collected. The walking training program achieved significant velocity (χ² = 126.38, p < 0.001) and step length (χ² = 27.27, p = 0.001) improvements in PG. Differences in improvement between PG and CG in terms of velocity (χ² = 7.089, df = 1, p = 0.008) and step length (χ² = 7.718, df = 1, p = 0.005) were also identified. CONCLUSION: The applicability of this 12-week walking program both for PD patients and community-dwelling older adults was identified. Conducting the economic evaluation and neurology studies of the 12-week walking program and test the effects of five-week walking program are suggested.

Nitric oxide reduces blood pressure in the nucleus tractus solitarius: a real time electrochemical study.

Increasing evidence has demonstrated that nitric oxide (NO) is involved in central cardiovascular regulation. In this study, we directly measured extracellular NO levels, in real-time, in the nucleus tractus solitarius (NTS) of anesthetized cats using Nafion/Porphyrine/o-Phenylenediamine-coated NO sensors. We found that local application of L-arginine (L-Arg) induced NO overflow in NTS and hypotension. These responses were potentiated in the vagotomized animals. Pretreatment with NO synthase (NOS)/guanylate cyclase inhibitor methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or NO scavenger hemoglobin attenuated L-Arg-induced hypotension, suggesting that exogenous supplement of NO suppressed cardiac functions through the NOS/cyclic guanosine monophosphate mechanism. The role of endogenous NO was examined after local application of N(G)-nitro-L-arginine methyl ester (L-NAME). We found that L-NAME suppressed endogenous NO levels in NTS and elicited hypertension and tachycardia. Taken together, our data suggest that NO is tonically released in the NTS to inhibit blood pressure.

Electrochemical studies of the effects of substance P on dopamine terminals in the rat striatum.

The purpose of this study was to investigate the regulation of dopamine (DA) release and clearance by Substance P (SP) in striatum. In vivo high speed chronoamperometric recording techniques, with Nafion-coated carbon-fiber electrodes, were used to evaluate extracellular DA concentrations in urethane-anesthetized Sprague-Dawley rats. SP was locally applied to striatum. Our data indicate that SP can induce DA release in striatum. However, only about half of the striatal sites respond to SP. Readministration of SP to the same site elicited a smaller DA release. These data suggest that SP-evoked release shows tachyphyllaxis and is heterogeneous in the striatum. Lesioning of DA neurons with 6-OHDA into the medial forebrain bundle abolished DA release induced by SP. It has been shown that SP interacts with three different tachykinin receptors. We found that application of the Neurokinin-1 (NK1) agonist [Sar9, Met (O2)11]SP, but not the NK3 agonist senktide, induced DA release, suggesting that SP-induced DA release may be mediated through NK1 receptors. We further examined SP effects on DA clearance in striatum. We found that pretreatment with SP significantly attenuated extracellular levels of DA after exogeneous application of DA, suggesting that DA clearance is augmented by SP. Taken together, our data demonstrate that substance P facilitates dopamine release and clearance in the striatum.

Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial cell line-derived neurotrophic factor restore dopamine release in the striatum of 6-hydroxydopamine-lesioned rats.

We have previously reported that grafting of fetal ventral mesencephalic (VM) tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF) injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase (TH) immunoreactivity. In this study, we investigated the electrochemical indices of dopamine (DA) release in these grafted animals in the striatum and nigra. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. One to two months after 6-OHDA administration, fetal VM tissues were grafted in the lesioned nigral area followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals receiving transplantation and GDNF, but not BDNF or PBS, injection showed a significant decrease in rotation 1-3 months after grafting. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate DA overflow in the striatum. We found that 6-OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane-anesthetized rats. Three months after GDNF-bridged grafting, application of KCl elicited DA release both in nigra and striatum. The KCl-evoked DA release area was limited to the GDNF-bridging tract in the striatum. On the other hand, KCl did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical studies indicated that TH-positive neurons and fibers were found in the nigra and striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal nigral transplantation and GDNF injection may restore the nigrostriatal DA pathway and DA release in these hemiparkinsonian animals and support the hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA neurons.

Differential sensitivity of dopamine release and clearance to 6-hydroxydopamine lesioning in rat striatum.

In the present study, we compared the changes in dopamine (DA) release and clearance in the striatum after unilateral 6-hydroxydopamine (6- OHDA) lesioning of the nigrostriatal DA pathway in urethane-anesthetized rats. High-speed in vivo chronoamperometric recording techniques using Nafion-coated carbon fiber electrodes were used to evaluate extracellular DA concentration. We found that DA release, induced by local KCl application in the striatum, was maximally suppressed 21 days after lesioning. DA clearance was also affected; however, the maximal effect occurred much earlier than changes in DA release. We found that 3-7 days after lesioning, extracellular DA concentration was significantly higher in the lesioned striatum after locally applying DA. Local application of nomifensine, which blocks high affinity DA uptake, did not further potentiate the amplitude and duration of DA overflow in these animals, suggesting that the high affinity uptake of DA was abolished 3-7 days after 6-OHDA lesioning. In conclusion, our data suggest that the time courses of changes in clearance and the release of DA are differentially affected by this selective neurotoxin.

Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro.

The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2-29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1-46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was -106.9 +/- 1.7 mV (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the alpha 1-, alpha 2B- and alpha 2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10-300 nM), an alpha 2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to alpha 2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K+ channels, resulting in the observed hyperpolarization of the membrane.