Increased Homer1-mGluR5 mediates chronic stress-induced depressive-like behaviors and glutamatergic dysregulation via activation of PERK-eIF2α.

Glutamatergic dysregulation has served as one common pathophysiology of major depressive disorder (MDD) and a promising target for treatment intervention. Previous studies implicate neurotransmission via metabotropic glutamate receptors (mGluRs) and Homer1 in stress-induced anhedonia, but the mechanisms have not been well elucidated. In the present study, we used two different animal models of depression, chronic social defeat stress (CSDS) and chronic restraint stress (CRS), to investigate the expression of Homer1 isoforms and functional interaction with mGluRs. We found that chronic stress selectively upregulated the expression of Homer1b/c in the hippocampus, whereas the level of Homer1a was unchanged. Additionally, there was a significant negative correlation between the levels of Homer1-mGluR5 signaling and depressive-like behaviors. Both application of paired-pulse low-frequency stimulation (PP-LFS) and the selective group 1 mGluRs agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) significantly enhanced mGluR-dependent long-term depression (LTD) at CA3-CA1 pyramidal cell synapses in slices from susceptible mice, whereas there was no change in NMDAR-dependent LTD induced by LFS. Furthermore, these effects were associated with the internalization of surface AMPARs in hippocampal pyramidal neurons, including reduced the expression of AMPARs and amplitude of AMPARs-mediated mEPSC. Finally, we found that chronic stress activated the KR-like ER kinase-eukaryotic initiation factor 2α (PERK-eIF2α) signaling pathway, subsequently phosphorylated cAMP response element binding protein (CREB) at the S129 and reduced the BDNF level, eventually leading to the impairment of synaptic transmission and depressive-like behaviors. Therefore, our study suggests that PERK-eIF2α acts as a critical target downstream of Homer1-mGluR5 complex to mediate chronic stress-induced depressive-like behaviors, and highlights them as a potential target for the treatment of mood disorder.

Pulsed radiofrequency to the great occipital nerve for the treatment of intractable postherpetic itch: a case report.

A patient with intractable postherpetic itch lasting for 1 year was reported. The itch was mainly from the left vertex, frontal and ophthalmic regions and extended to the left neck area. The patient had negative response to the ophthalmic nerve block. Under the initial positive response to the great occipital nerve block, pulsed radiofrequency (PRF) was performed on the position of the great occipital nerve. After 4 months treatment, the itch was completely vanished. This case study demonstrates the effectiveness of PRF for intractable postherpetic itch originating in the head and neck. However, more samples needed to verify this management.

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 Parkinson's 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.

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.

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 Parkinson's 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.