Payam Dibaj | Max-Planck-Institut - Academia.edu (original) (raw)
Papers by Payam Dibaj
Physiological Research, Jun 21, 2017
We developed appropriate surgical procedures for single and repetitive multi-photon imaging of sp... more We developed appropriate surgical procedures for single and repetitive multi-photon imaging of spinal cord in vivo. By intravenous anesthesia, artificial ventilation and laminectomy, acute experiments were performed in the dorsal and lateral white matter. By volatile anesthesia and minimal-invasive surgery, chronic repetitive imaging up to 8 months was performed in the dorsal column through the window between two adjacent spines. Transgenic mouse technology enabled simultaneous imaging of labeled axons, astrocytes and microglia. Repetitive imaging showed positional shifts of microglia over time. These techniques serve for investigations of cellular dynamics and cell-cell interactions in intact and pathologically changed spinal tissue.
Klinische Neurophysiologie, Jul 20, 2012
• ▶ amyotrophic lateral sclerosis • ▶ in vivo imaging • ▶ 2-photon laser-scanning microscopy • ▶ ... more • ▶ amyotrophic lateral sclerosis • ▶ in vivo imaging • ▶ 2-photon laser-scanning microscopy • ▶ glial cells • ▶ microgilia • ▶ nitric oxide (nitrogen monoxide, NO
Intracranial hypotension due to a large thoracic meningocele
Deutsches Arzteblatt International, Mar 17, 2023
bioRxiv (Cold Spring Harbor Laboratory), Feb 25, 2022
Neuronal functions and impulse propagation depend on the continuous supply of glucose 1,2. Surpri... more Neuronal functions and impulse propagation depend on the continuous supply of glucose 1,2. Surprisingly, the mammalian brain has no obvious energy stores, except for astroglial glycogen granules 3. Oligodendrocytes make myelin for rapid axonal impulse conduction 4 and also support axons metabolically with lactate 5-7. Here, we show that myelin itself, a lipid-rich membrane compartment, becomes a local energy reserve when glucose is lacking. In the mouse optic nerve, a model white matter tract, oligodendrocytes survive glucose deprivation far better than astrocytes, by utilizing myelin lipids which requires oxygen and fatty acid beta-oxidation. Importantly, fatty acid oxidation also contributes to axonal ATP and basic conductivity. This metabolic support by fatty acids is an oligodendrocyte function, involving mitochondria and myelin-associated peroxisomes, as shown with mice lacking Mfp2. To study reduced glucose availability in vivo without physically starving mice, we deleted the Slc2a1 gene from mature oligodendrocytes. This caused a significant decline of the glucose transporter GLUT1 from the myelin compartment leading to myelin sheath thinning. We suggest a model in which myelin turnover under low glucose conditions can transiently buffer axonal energy metabolism. This model may explain the gradual loss of myelin in a range of neurodegenerative diseases 8 with underlying hypometabolism 9. Main Oligodendrocytes are glycolytic cells that can provide myelinated axons with lactate or pyruvate for the generation of ATP 5,6,10. Surprisingly, Drosophila revealed that the metabolic support of axons by associated glia preceded the evolution of myelin in vertebrates 11,12. In non-myelinating species, notably in Drosophila larvae 13,14 and in lamprey 15 , the axonassociated glial cells that lack myelin accumulate lipid droplets, which are well-known energy reserves 16,17. We therefore hypothesized that lipid droplets, which are not a feature of mammalian oligodendrocytes 18 , were 'replaced' in vertebrate evolution by the exuberant synthesis of lipid-rich membranes as myelin 19. Spirally wrapped around axons, these myelin membranes enable saltatory impulse propagation 20 and block ephaptic coupling between neighboring axons 12. If myelin had indeed replaced lipid droplets, we reasoned it is possible that myelin has retained a function in energy metabolism. Glial cell survival in the absence of glucose Cultured cells can die rapidly without glucose 21,22. We therefore asked whether myelinating oligodendrocytes, when glucose deprived, can metabolize myelin lipids for survival. We chose the acutely isolated optic nerve (Fig.1a) as a model system, in which glial cells survive when provided with glucose (or lactate) and oxygen. We analyzed fully myelinated transgenic mice at age 2 months, expressing fluorescent proteins in mature oligodendrocytes (Cnp-mEos2
成NEX-CreERT2マウスにおける錐体ニューロンのin vivoイメージングおよび非侵襲的アブレーション | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Cerebral Cortex, 2012
成NEX-CreERT2マウスにおける錐体ニューロンのin vivoイメージングおよび非侵襲的アブレーション
Cerebral Cortex, 2012
Physiological Research, Feb 14, 2013
Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which p... more Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K + channels (Kir channels) are potential candidate proteins to hyperpolarize neuronal cell membranes. However, heterologous expression of inwardly-rectifying K + channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC-34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC-34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K + currents as well as hyperpolarization of the cell membrane was observed in Kir4.1-transfected cells. Na + inward currents, observed in NSC-34 controls, were absent in Kir4.1/EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologous expression of a weakly inward-rectifying K + channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more gliallike phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms.
In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a co... more In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in p...
Chronic muscle pain facilitates bilateral flexion reflex pattern in the feline spinal cord
Hemifacial spasm through changes of cerebrospinal fluid pressure in idiopathic intracranial hypertension
Baylor University Medical Center Proceedings
Microglial reaction to spinal cord injury and axonal degeneration. An in vivo laser scanning microscopy study in mice
Translational Psychiatry, 2020
The transcription factor TCF4 was confirmed in several large genome-wide association studies as o... more The transcription factor TCF4 was confirmed in several large genome-wide association studies as one of the most significant schizophrenia (SZ) susceptibility genes. Transgenic mice moderately overexpressing Tcf4 in forebrain (Tcf4tg) display deficits in fear memory and sensorimotor gating. As second hit, we exposed Tcf4tg animals to isolation rearing (IR), chronic social defeat (SD), enriched environment (EE), or handling control (HC) conditions and examined mice with heterozygous deletion of the exon 4 (Tcf4Ex4δ+/−) to unravel gene-dosage effects. We applied multivariate statistics for behavioral profiling and demonstrate that IR and SD cause strong cognitive deficits of Tcf4tg mice, whereas EE masked the genetic vulnerability. We observed enhanced long-term depression in Tcf4tg mice and enhanced long-term potentiation in Tcf4Ex4δ+/− mice indicating specific gene-dosage effects. Tcf4tg mice showed higher density of immature spines during development as assessed by STED nanoscopy an...
eLife, 2019
Myelin serves as an axonal insulator that facilitates rapid nerve conduction along axons. By tran... more Myelin serves as an axonal insulator that facilitates rapid nerve conduction along axons. By transmission electron microscopy, a healthy myelin sheath comprises compacted membrane layers spiraling around the cross-sectioned axon. Previously we identified the assembly of septin filaments in the innermost non-compacted myelin layer as one of the latest steps of myelin maturation in the central nervous system (CNS) (Patzig et al., 2016). Here we show that loss of the cytoskeletal adaptor protein anillin (ANLN) from oligodendrocytes disrupts myelin septin assembly, thereby causing the emergence of pathological myelin outfoldings. Since myelin outfoldings are a poorly understood hallmark of myelin disease and brain aging we assessed axon/myelin-units in Anln-mutant mice by focused ion beam-scanning electron microscopy (FIB-SEM); myelin outfoldings were three-dimensionally reconstructed as large sheets of multiple compact membrane layers. We suggest that anillin-dependent assembly of sept...
Nature Communications, 2017
Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure ... more Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.
Cell Reports, 2014
Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. I... more Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an ''optimal'' level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.
Neurology International, 2021
A 60-year-old man suffering from recurrent attacks of yawning-fatigue-syndrome, triggered by mild... more A 60-year-old man suffering from recurrent attacks of yawning-fatigue-syndrome, triggered by mild exercise of his right leg since a temporary lumbar disc herniation 9 years ago, was initially treated with the oral µ-opioid-receptor agonist tilidine before each bout of exercise (see Dibaj et al. 2019 JAMA Neurology 2019;77:254). During the first few months, this treatment continuously prolonged the time without exercise-triggered yawning and fatigue. In the next few months of treatment, exercise was increased in a graded manner to alleviate the yawning-fatigue-syndrome. The number of repetitions of the physical exercises was gradually increased without taking the opioid beforehand. After several months, almost the same effort level without medication could be achieved by graded activity as before under the influence of opioid medication. Graded physical activity can thus disrupt complex pathophysiological mechanisms leading to yawning and fatigue.
Lyme Neuroborreliosis with Long Meningeal Enhancement and Ischemic Stroke
European Neurology
aCenter for Rare Diseases Göttingen, University Medical Center Göttingen, Georg August University... more aCenter for Rare Diseases Göttingen, University Medical Center Göttingen, Georg August University, Göttingen, Germany; bMax-Planck-Institute for Experimental Medicine, Göttingen, Germany; cCenter for Neurology, Asklepios Hospitals Schildautal, Seesen, Germany; dDepartment of Radiology, Asklepios Hospitals Schildautal, Seesen, Germany Received: March 26, 2020 Accepted: May 7, 2020 Published online: July 15, 2020
Physiological Research
Anesthetic and surgical procedures and an electrophysiological method were developed for recordin... more Anesthetic and surgical procedures and an electrophysiological method were developed for recording nerve conduction velocity (NCV) of CNS fibers in the murine spinal cord. Under intravenous anesthesia and artificial ventilation the lumbar spinal cord segments L1 to L4 and dorsal roots L3 to L5 on the left side were exposed by laminectomy. After stimulation of the dorsal root L4, a compound action potential (CAP) was recorded at the ipsilateral left fasciculus gracilis at the spinal cord level L1. The latency from stimulation to the CAP together with the measured distance between the electrodes was used for the determination of the NCV. NCV of the fastest fibers in the fasciculus gracilis was observed to be approximately 28 m/s. Reversible decrease of the NCV was measured, in vivo, under general hypothermia. The technique described serves for in vivo electrophysiological investigations of spinal central fibers in wildtype and mutant mice.
Author response: Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction
Physiological Research, Jun 21, 2017
We developed appropriate surgical procedures for single and repetitive multi-photon imaging of sp... more We developed appropriate surgical procedures for single and repetitive multi-photon imaging of spinal cord in vivo. By intravenous anesthesia, artificial ventilation and laminectomy, acute experiments were performed in the dorsal and lateral white matter. By volatile anesthesia and minimal-invasive surgery, chronic repetitive imaging up to 8 months was performed in the dorsal column through the window between two adjacent spines. Transgenic mouse technology enabled simultaneous imaging of labeled axons, astrocytes and microglia. Repetitive imaging showed positional shifts of microglia over time. These techniques serve for investigations of cellular dynamics and cell-cell interactions in intact and pathologically changed spinal tissue.
Klinische Neurophysiologie, Jul 20, 2012
• ▶ amyotrophic lateral sclerosis • ▶ in vivo imaging • ▶ 2-photon laser-scanning microscopy • ▶ ... more • ▶ amyotrophic lateral sclerosis • ▶ in vivo imaging • ▶ 2-photon laser-scanning microscopy • ▶ glial cells • ▶ microgilia • ▶ nitric oxide (nitrogen monoxide, NO
Intracranial hypotension due to a large thoracic meningocele
Deutsches Arzteblatt International, Mar 17, 2023
bioRxiv (Cold Spring Harbor Laboratory), Feb 25, 2022
Neuronal functions and impulse propagation depend on the continuous supply of glucose 1,2. Surpri... more Neuronal functions and impulse propagation depend on the continuous supply of glucose 1,2. Surprisingly, the mammalian brain has no obvious energy stores, except for astroglial glycogen granules 3. Oligodendrocytes make myelin for rapid axonal impulse conduction 4 and also support axons metabolically with lactate 5-7. Here, we show that myelin itself, a lipid-rich membrane compartment, becomes a local energy reserve when glucose is lacking. In the mouse optic nerve, a model white matter tract, oligodendrocytes survive glucose deprivation far better than astrocytes, by utilizing myelin lipids which requires oxygen and fatty acid beta-oxidation. Importantly, fatty acid oxidation also contributes to axonal ATP and basic conductivity. This metabolic support by fatty acids is an oligodendrocyte function, involving mitochondria and myelin-associated peroxisomes, as shown with mice lacking Mfp2. To study reduced glucose availability in vivo without physically starving mice, we deleted the Slc2a1 gene from mature oligodendrocytes. This caused a significant decline of the glucose transporter GLUT1 from the myelin compartment leading to myelin sheath thinning. We suggest a model in which myelin turnover under low glucose conditions can transiently buffer axonal energy metabolism. This model may explain the gradual loss of myelin in a range of neurodegenerative diseases 8 with underlying hypometabolism 9. Main Oligodendrocytes are glycolytic cells that can provide myelinated axons with lactate or pyruvate for the generation of ATP 5,6,10. Surprisingly, Drosophila revealed that the metabolic support of axons by associated glia preceded the evolution of myelin in vertebrates 11,12. In non-myelinating species, notably in Drosophila larvae 13,14 and in lamprey 15 , the axonassociated glial cells that lack myelin accumulate lipid droplets, which are well-known energy reserves 16,17. We therefore hypothesized that lipid droplets, which are not a feature of mammalian oligodendrocytes 18 , were 'replaced' in vertebrate evolution by the exuberant synthesis of lipid-rich membranes as myelin 19. Spirally wrapped around axons, these myelin membranes enable saltatory impulse propagation 20 and block ephaptic coupling between neighboring axons 12. If myelin had indeed replaced lipid droplets, we reasoned it is possible that myelin has retained a function in energy metabolism. Glial cell survival in the absence of glucose Cultured cells can die rapidly without glucose 21,22. We therefore asked whether myelinating oligodendrocytes, when glucose deprived, can metabolize myelin lipids for survival. We chose the acutely isolated optic nerve (Fig.1a) as a model system, in which glial cells survive when provided with glucose (or lactate) and oxygen. We analyzed fully myelinated transgenic mice at age 2 months, expressing fluorescent proteins in mature oligodendrocytes (Cnp-mEos2
成NEX-CreERT2マウスにおける錐体ニューロンのin vivoイメージングおよび非侵襲的アブレーション | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Cerebral Cortex, 2012
成NEX-CreERT2マウスにおける錐体ニューロンのin vivoイメージングおよび非侵襲的アブレーション
Cerebral Cortex, 2012
Physiological Research, Feb 14, 2013
Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which p... more Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K + channels (Kir channels) are potential candidate proteins to hyperpolarize neuronal cell membranes. However, heterologous expression of inwardly-rectifying K + channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC-34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC-34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K + currents as well as hyperpolarization of the cell membrane was observed in Kir4.1-transfected cells. Na + inward currents, observed in NSC-34 controls, were absent in Kir4.1/EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologous expression of a weakly inward-rectifying K + channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more gliallike phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms.
In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a co... more In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in p...
Chronic muscle pain facilitates bilateral flexion reflex pattern in the feline spinal cord
Hemifacial spasm through changes of cerebrospinal fluid pressure in idiopathic intracranial hypertension
Baylor University Medical Center Proceedings
Microglial reaction to spinal cord injury and axonal degeneration. An in vivo laser scanning microscopy study in mice
Translational Psychiatry, 2020
The transcription factor TCF4 was confirmed in several large genome-wide association studies as o... more The transcription factor TCF4 was confirmed in several large genome-wide association studies as one of the most significant schizophrenia (SZ) susceptibility genes. Transgenic mice moderately overexpressing Tcf4 in forebrain (Tcf4tg) display deficits in fear memory and sensorimotor gating. As second hit, we exposed Tcf4tg animals to isolation rearing (IR), chronic social defeat (SD), enriched environment (EE), or handling control (HC) conditions and examined mice with heterozygous deletion of the exon 4 (Tcf4Ex4δ+/−) to unravel gene-dosage effects. We applied multivariate statistics for behavioral profiling and demonstrate that IR and SD cause strong cognitive deficits of Tcf4tg mice, whereas EE masked the genetic vulnerability. We observed enhanced long-term depression in Tcf4tg mice and enhanced long-term potentiation in Tcf4Ex4δ+/− mice indicating specific gene-dosage effects. Tcf4tg mice showed higher density of immature spines during development as assessed by STED nanoscopy an...
eLife, 2019
Myelin serves as an axonal insulator that facilitates rapid nerve conduction along axons. By tran... more Myelin serves as an axonal insulator that facilitates rapid nerve conduction along axons. By transmission electron microscopy, a healthy myelin sheath comprises compacted membrane layers spiraling around the cross-sectioned axon. Previously we identified the assembly of septin filaments in the innermost non-compacted myelin layer as one of the latest steps of myelin maturation in the central nervous system (CNS) (Patzig et al., 2016). Here we show that loss of the cytoskeletal adaptor protein anillin (ANLN) from oligodendrocytes disrupts myelin septin assembly, thereby causing the emergence of pathological myelin outfoldings. Since myelin outfoldings are a poorly understood hallmark of myelin disease and brain aging we assessed axon/myelin-units in Anln-mutant mice by focused ion beam-scanning electron microscopy (FIB-SEM); myelin outfoldings were three-dimensionally reconstructed as large sheets of multiple compact membrane layers. We suggest that anillin-dependent assembly of sept...
Nature Communications, 2017
Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure ... more Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.
Cell Reports, 2014
Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. I... more Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an ''optimal'' level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.
Neurology International, 2021
A 60-year-old man suffering from recurrent attacks of yawning-fatigue-syndrome, triggered by mild... more A 60-year-old man suffering from recurrent attacks of yawning-fatigue-syndrome, triggered by mild exercise of his right leg since a temporary lumbar disc herniation 9 years ago, was initially treated with the oral µ-opioid-receptor agonist tilidine before each bout of exercise (see Dibaj et al. 2019 JAMA Neurology 2019;77:254). During the first few months, this treatment continuously prolonged the time without exercise-triggered yawning and fatigue. In the next few months of treatment, exercise was increased in a graded manner to alleviate the yawning-fatigue-syndrome. The number of repetitions of the physical exercises was gradually increased without taking the opioid beforehand. After several months, almost the same effort level without medication could be achieved by graded activity as before under the influence of opioid medication. Graded physical activity can thus disrupt complex pathophysiological mechanisms leading to yawning and fatigue.
Lyme Neuroborreliosis with Long Meningeal Enhancement and Ischemic Stroke
European Neurology
aCenter for Rare Diseases Göttingen, University Medical Center Göttingen, Georg August University... more aCenter for Rare Diseases Göttingen, University Medical Center Göttingen, Georg August University, Göttingen, Germany; bMax-Planck-Institute for Experimental Medicine, Göttingen, Germany; cCenter for Neurology, Asklepios Hospitals Schildautal, Seesen, Germany; dDepartment of Radiology, Asklepios Hospitals Schildautal, Seesen, Germany Received: March 26, 2020 Accepted: May 7, 2020 Published online: July 15, 2020
Physiological Research
Anesthetic and surgical procedures and an electrophysiological method were developed for recordin... more Anesthetic and surgical procedures and an electrophysiological method were developed for recording nerve conduction velocity (NCV) of CNS fibers in the murine spinal cord. Under intravenous anesthesia and artificial ventilation the lumbar spinal cord segments L1 to L4 and dorsal roots L3 to L5 on the left side were exposed by laminectomy. After stimulation of the dorsal root L4, a compound action potential (CAP) was recorded at the ipsilateral left fasciculus gracilis at the spinal cord level L1. The latency from stimulation to the CAP together with the measured distance between the electrodes was used for the determination of the NCV. NCV of the fastest fibers in the fasciculus gracilis was observed to be approximately 28 m/s. Reversible decrease of the NCV was measured, in vivo, under general hypothermia. The technique described serves for in vivo electrophysiological investigations of spinal central fibers in wildtype and mutant mice.
Author response: Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction