The Cortisol Awakening Response in Patients with Poststroke Depression Is Blunted and Negatively Correlated with Depressive Mood.

It is important to reduce poststroke depression (PSD) to improve the stroke outcomes and quality of life in stroke patients, but the underlying mechanisms of PSD are not completely understood. As many studies implicate dysregulation of hypothalamic-pituitary-adrenal axis in the etiology of major depression and stroke, we compared the cortisol awakening response (CAR) of 28 admitted PSD patients with that of 23 age-matched caregiver controls. Saliva samples for cortisol measurement were collected immediately, 15, 30, and 45 min after awakening for two consecutive days. Depressive mood status in PSD patients was determined with Beck Depression Inventory and Hamilton Depression Rating Scale. Salivary cortisol levels of PSD patients did not rise significantly at any sampling time, showing a somewhat flat curve. Caregiver controls showed significantly higher CAR at 15 and 30 min after awakening compared to PSD patients even though the two groups did not differ at awakening or 45 min after awakening. Area-under-the-curve analysis revealed a significant negative correlation between the CAR and the degree of depression in PSD patients. Thus, our findings suggest that poststroke depression is closely related with dysfunctional HPA axis indicated by blunted CAR.

Effects of electro-acupuncture therapy on post-stroke depression in patients with different degrees of motor function impairments: a pilot study.

[Purpose] The present study examined whether electro-acupuncture therapy reduces post-stroke depression (PSD) and whether motor function impairments interact with the effects of the therapy. [Subjects] Twenty-eight PSD patients were assessed and assigned to either a good or poor motor function group depending on their motor grade. [Methods] The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS) and Manual Muscle Test (MMT) were administered at the screening and initial phases of the study, and at the 4th, 8th, 12th and 16th week of the daily electro-acupuncture treatment. [Results] The electro-acupuncture treatment reduced PSD (as assessed by BDI and HDRS) of the patients. In particular, the depression of the good motor function group was significantly more reduced than that of the poor motor function group. The degree of motor function impairment did not change throughout the study in either group. [Conclusion] The results of the present study demonstrate that electro-acupuncture therapy can improve PSD, and that the treatment effect varies depending on the degree of motor function impairment.

RGS4 exerts inhibitory activities on the signaling of dopamine D2 receptor and D3 receptor through the N-terminal region.

Dopamine D(2) receptor and D(3) receptor (D(2)R and D(3)R) are the major targets for current antipsychotic drugs, and their proper regulation has pathological and pharmacological significance. This study was conducted to understand the functional roles and molecular mechanisms of RGS proteins (RGS2, RGS4, and RGS9-2) on the signaling of D(2)R and D(3)R. RGS proteins were co-expressed with D(2)R and D(3)R in HEK-293 cells. The protein interactions between RGS proteins and D(2)R/D(3)R, and effects of RGS proteins on the internalization, signaling, and desensitization of D(2)R/D(3)R were determined. In addition, the RGS4 proteins were subdivided into N-terminal region, RGS domain, and the C-terminal region, and the specific subdomain of RGS4 protein involved in the regulation of the signaling of D(2)R/D(3)R was determined. All of RGS proteins we tested interacted with D(2)R/D(3)R. RGS4 exerted potent inhibitory activities on the signaling of D(2)R/D(3)R. RGS9-2 exerted selective but moderate inhibitory activity on D(3)R and the internalization of D(2)R. RGS2 had no effect. The N-terminal domain of RGS4 was involved in its interaction with D(2)R and D(3)R and was required for the inhibitory activity of the RGS domain. The study for the first time showed that RGS4 is the major RGS protein which interacts through the N-terminal region and exerts potent inhibitory activities on the signaling of D(2)R and D(3)R.

Neural responses in rat brain during acute immobilization stress: a [F-18]FDG micro PET imaging study.

We used the [F-18]FDG micro PET neuroimaging technique to investigate changes in brain activity induced by acute stress in rats. Animals were given immobilization stress for 1 or 2 h, or 1-h stress followed by 1-h recovery, after which their brains were scanned. Plasma corticosterone levels measured at various time points in separate groups of rats showed a rapid increase during stress and slower decrease after termination of the stress. Immobilization stress given for an hour activated the hypothalamus, entorhinal and insular/piriform cortices, and raphe pallidus nucleus. At the same time, the dorsal hippocampus, thalamus, other cortical areas (motor, somatosensory and barrel field), striatum, superior colliculus and cerebellum were deactivated. With 2-h immobilization stress, the activity of the hypothalamus, various cortical areas and dorsal hippocampus habituated during the second hour while that of the thalamus and cerebellum did not. During 1-h recovery, the hypothalamic activation and widespread cortical deactivation disappeared, but the dorsal hippocampus, thalamus and cerebellum still remained significantly deactivated. Additional brain areas such as the septum and prelimbic cortex now showed deactivation during recovery. Changes in glucose metabolism in the dorsal hippocampus and hypothalamus exhibited a highly significant negative correlation, supporting the view that the hippocampus is involved in regulating the stress response of the hypothalamo-pituitary-adrenal axis. The advantages and limitations of the [F-18]FDG micro PET used in this study are discussed.

Effects of injections of glucose into the dorsal striatum on learning of place and response mazes.

The present experiment tested the hypothesis that facilitation of striatal function with intra-striatal glucose injections would facilitate learning a striatum-dependent response maze and impair learning a hippocampus-dependent place maze. Food-deprived Sprague-Dawley male rats were trained to find food in a Y-maze. In the place version of the maze, rats were rewarded for learning to go to an arm located in a fixed location while in the response task rats were rewarded for consistently turning in the same direction at the choice point. Artificial cerebrospinal fluid (1 microL) containing either 0.7 nmol of glucose (control) or 20 nmol of glucose was injected bilaterally into the dorsal striatum immediately before training. The animals were trained to a criterion of 9/10 correct choices. In the place maze, glucose injections impaired learning, as measured by number of trials required to reach 9/10 correct. However, in the response task, glucose injections did not enhance learning. A subsequent experiment examined the effects of intra-striatal glucose injections on acquisition of the response task under two different visual cue conditions, addition of an intra-maze light cue that predicted the correct arm or with removal of most visual extramaze cues. Glucose again failed to facilitate acquisition of the response task under these conditions. These findings suggest that facilitation of striatal function via intra-striatal glucose injections is sufficient to impair place learning but not to enhance response learning, perhaps separating the neurochemical mechanisms for striatal involvement in impairment of place and enhancement of response learning.