Rong-Chun Li

Deep brain stimulation of the pedunculopontine tegmental nucleus may influence renal function

Deep brain stimulation of the pedunculopontine tegmental nucleus (PPTg) had usually been reported to improve the symptoms of advanced Parkinsons disease. Previous studies showed that neurons in the PPTg involved in the control of the sympathetic outflow to the kidneys. Our recent studies using transneuronal labeling pseudorabies virus (PRV)-614 supported the sympathetic nature of the caudal PPTg. We propose a hypothesis that deep brain stimulation of the PPTg may influence renal function by serotonergic and catecholaminergic pathways. Because PRV-614/tryptophan hydroxylase and PRV-614/tyrosine hydroxylase double-labeled neurons in the compact parts of PPTg (cpPPTg) were not detected, deep brain stimulation of the cpPPTg might not influence renal function.

Laterodorsal tegmentum and pedunculopontine tegmental nucleus circuits regulate renal functions: Neuroanatomical evidence in mice models

Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.SummaryNeurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.

Role of Spinal Cord in Regulating Mouse Kidney: A Virally Mediated Trans-synaptic Tracing Study

OBJECTIVE To determine the spinal innervation and neuronal connections is important for studying renal metabolic responses. MATERIALS AND METHODS In this study, the spinal cords of 10 adult male C57BL/6J strain mice were mapped retrograde using injections of pseudorabies virus (PRV)-614. The virus, injected into the kidney, was specifically transported to the spinal cord. RESULTS At 5 days after injection of the PRV-614, PRV-614-positive cells were found in the intermediolateral cell column, the intercalates nucleus, or the central autonomic nucleus of spinal cord segments T4-L1, and most PRV-614-labeled cells were found in the T9 segment. CONCLUSION Our results revealed neuroanatomical circuits between kidney and the spinal intermediolateral cell column neurons.

Stimulation of the pedunculopontine tegmental nucleus may affect renal function by melanocortinergic signaling

Deep brain stimulation of the pedunculopontine tegmental nucleus (PPTg) has been reported to improve gait disturbance in animal models of Parkinsonism and among patients with Parkinsons disease. Evidence suggests that neurons in the PPTg are involved in the control of the sympathetic outflow to the kidneys, and sympathetic regulation is a major component of central melanocortin action. Our recent studies using transneuronal labeling pseudorabies virus (PRV)-614 and melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) transgenic mice supported the melanocortinergic nature of the middle and caudal PPTg (mPPTg and cPPTg). Because PRV-614/MC4R-GFP double-labeled neurons in the mPPTg and cPPTg were detected, we propose a hypothesis that deep brain stimulation of the PPTg may influence renal function by the melanocortinergic pathway.

The optimal acupoint for acupuncture stimulation as a complementary therapy in pediatric epilepsy

Fig. 1. Diagrams of the locations of auricular acupuncture points (Shen Men). It is well known that the auricular branch of the vagus nerve innervates the auricular concha and so provides noninvasive or minimally invasive access to the vagus nerve [47]. Wang et al. [48] had demonstrated the use of ear acupuncture (Shen Men) for preoperative anxiety by placing a needle in the concha, an area innervated by the vagus nerve. Metaphysical theories of “auriculotherapy” claim that 168 body points on the ear are connected to various body locations. The optimal acupoint for acupuncture stimulation as a complementary therapy in pediatric epilepsy

The mechanism of electroacupuncture for predicting the efficacy of deep brain stimulation in pharmacoresistant epilepsy may be involved in the melanocortinergic signal

Intractable epilepsy is still one of the most confusing and enigmatic neurological disorders [1,2]. Deep brain stimulation targeted at the subthalamic nucleus (STN-DBS) is an alternative treatment for patients with uncontrolled symptoms of epilepsy [3], but predicting outcome before the operation is not possible. Electrical stimulation at acupoints was also efficient in treating medically refractory epilepsy, and Yan et al. and Meng et al. suggested that electroacupuncture at acupoints could predict the curative effect of STN-DBS for refractory epilepsy [4,5]. However, but the mechanisms of electroacupuncture for predicting the efficacy of electrical stimulation in pharmacoresistant epilepsy are still unclear. It is interesting to note that previous studies have demonstrated that epileptic seizures are tightly linked to an imbalance between the excitatory [glutamate (Glu), aspartate (Asp)] and inhibitory [GABA, glycine (Gly), and taurine (Tau)] neuronal transmitters [6]. Otherwise, it has been verified that the therapeutic mechanism of STN-DBS and electroacupuncture at acupoints is associated with the balance between the excitatory and inhibitory neuronal transmitters [7,8]. Accordingly, some authors suggested that the mechanism of electroacupuncture for predicting the efficacy of deep brain stimulation in pharmacoresistant epilepsy involved the metabolism of amino acids [4,5]. We would like to further discuss the possible mechanism of electroacupuncture for predicting the efficacy of deep brain stimulation in MC4R-GFP transgenic mice [9–12]. As data have accumulated over the last two decades, STN-DBS is now identified as an importantmodification of energymetabolism as reflected by changes in daily energy metabolism after stimulation surgery [13]. The study of Batisse-Lignier et al. [14] indicated that STN-DBS in patients affected glucose disposal of endogenous glucose production, suggesting that a cross talk between the central subthalamic nucleus and peripheral tissues may regulate glucose homeostasis. In addition, clinical findings have demonstrated that the therapeutic mechanisms of STN-DBS are closely related to the changes in cerebral glucosemetabolism [15,16]. Some neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) had revealed that glucose metabolism significantly increased in the left superior medial frontal gyrus, the middle frontal gyrus, and the right superior medial frontal gyrus following electroacupuncture at Hegu (LI 4) and Quchi (LI 11) [17,18], suggesting that the clinical effect of electroacupuncture at acupoints is also related to the changes in cerebral glucose metabolism. Therefore, we presume that the possible mechanism of electroacupuncture for predicting the efficacy of deep brain stimulation in pharmacoresistant epilepsy may be involved in the changes in cerebral glucose metabolism.

The optimal segment for spinal cord stimulation in intractable epilepsy: A virally mediated transsynaptic tracing study in spinally transected transgenic mice

Several lines of evidence have indicated the success of spinal cord stimulation (SCS) for the treatment of movement disorders and pain [1–5]. Because advantages of reversibility and adjustability exist, SCS is expected to have therapeutic effects for patients with intractable epilepsy [6]. Studies in rodents have highlighted that SCS, consisting of electrical stimulation of the dorsal spinal cord using epidural electrodes, has been shown to achieve seizure remission [6,7]. However, the exact location of the optimal spinal segment for stimulation is not fully understood. It is well known that two main segments for stimulation are used: the high cervical and the upper thoracic epidural space. Nevertheless, it is still unclear whether the high cervical or the upper thoracic segment is tightly linked to the benefits of spinal stimulation in intractable epilepsy. The sympathetic or motor regulation of the spinal cord is known to be involved in the neuroplasticity and synaptic connectivity mechanisms of stimulation for several different movement disorders, such as neuropsychiatric disorders, intractable pain, and Parkinsons disease [8–10]. A number of studies have verified that the pseudorabies virus (PRV) technique provides a highly specific method of tracing polysynaptic pathways, and it has been used to map the sympathetic and motor pathways [11–16]. We explored the hypothesis that the functional integrity of synapses in the upper thoracic segment is essential to both sympathetic and motor projections, whereas that in the high cervical segment is not essential to sympathetic projection. We had characterized projections from the left gastrocnemius muscle to the intermediolateral cell column (IML) of the upper thoracic spinal cord in spinally transected [16] transgenic mice by using retrograde tracing techniques of transgenic recombinants of an attenuated PRV strain, PRV-614, expressing a novel monomeric red fluorescent protein (mRFP1) under the control of the cytomegalovirus immediate-early promoter, for direct visualization under a fluorescence microscope [17–19]. We found that injection of PRV-614 into the gastrocnemius muscle resulted in retrograde infection of neurons in the IML of the upper thoracic spinal cord (Fig. 1D), a finding which was in agreement with that of a previous immunohistochemical study investigating the IML of the thoracic cord that controlled the adrenal gland through the transneuronal tracer PRV-Bartha [15], suggesting that direct sympathetic neuronal circuits exist in the upper thoracic spinal cord. Consistent with previously published reports [17,20–22], sympathetic preganglionic neurons connected to the stomach, kidney, liver, and adrenal glands via transneuronal tracing of multisynaptic