Effects of Nerve Growth Factor on Axonal Retrograde Transport after Axonal Injury of Motoneurons

In this experimental study we coupled nerve growth factor (NGF) with notatin by dicyclohexylcarbodiimide to label NGF and observed the effects of NGF on axonal retrograde transport after axonal injury of motoneurons with the aid of notatin chemiluminescence system. The results showed that NGF could be transported through axon not only to sensory neurons in dorsal root ganglia but also to motoneurons in spinal cord ventral horn.

Security breach:peripheral nerves provide unrestricted access for toxin delivery into the central nervous system

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport.This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis.We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.

Regenerative peripheral nerve interface prevents neuroma formation after peripheral nerve transection

Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain.Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic.However,no reports have investigated the underlying mechanisms,and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date.In this study,we established a rat model of left sciatic nerve transfection,and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle.Results showed that,compared with rats subjected to nerve stump implantation inside the muscle,rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons,lower expressions of the fibrosis markerα-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump,lower autophagy behaviors,lower expressions of c-fos and substance P,higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia.These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.

The retromer component SNX6 interacts with dynactin p150Glued and mediates endosome-to-TGN transport

The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network （TGN）. It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins （SNXs）. Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2＇s dimerization partners, SNX6, interacts with the p150Gued subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-pl50Gued interaction. Disruption of the SNX6-pl50Glued interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.

Distribution of serotonin and FMRF-amide in the brain of Lymnaea stagnalis with respect to the visual system

Despite serotonin’s and FMRF-amide’s wide distribution in the nervous system of invertebrates and their importance as neurotransmitters,the exact roles they play in neuronal networks leaves many questions.We mapped the presence of serotonin and FMRF-amide-immunoreactivity in the central nervous system and eyes of the pond snail Lymnaea stagnalis and interpreted the results in connection with our earlier findings on the central projections of different peripheral nerves.Since the chemical nature of the intercellular connections in the retina of L.stagnalis is still largely unknown,we paid special attention to clarifying the role of serotonin and FMRF-amide in the visual system of this snail and compared our findings with those reported from other species.At least one serotonin-and one FMRF-amidergic fibre were labeled in each optic nerve,and since no cell bodies in the eye showed immunoreactivity to these neurotransmitters,we believe that efferent fibres with somata located in the central ganglia branch at the base of the eye and probably release 5HT and FMRF-amide as neuro-hormones.Double labelling revealed retrograde transport of neurobiotin through the optic nerve,allowing us to conclude that the central pathways and serotonin-and FMRF-amide-immunoreactive cells and fibres have different locations in the CNS in L.stagnalis.The chemical nature of the fibres,which connect the two eyes in L.stagnalis,is neither serotoninergic nor FMRF-amidergic.

Distribution of serotonin and FMRF-amide in the brain of Lymnaea stagnalis with respect to the visual system

Despite serotonin’s and FMRF-amide’s wide distribution in the nervous system of invertebrates and their importance as neurotransmitters, the exact roles they play in neuronal networks leaves many questions. We mapped the presence of serotonin and FMRF-amide-immunoreactivity in the central nervous system and eyes of the pond snail Lymnaea stagnalis and interpreted the results in connection with our earlier findings on the central projections of different peripheral nerves. Since the chemical nature of the intercellular connections in the retina of Lymnaea stagnalis is still largely unknown, we paid special attention to clarifying the role of serotonin and FMRF-amide in the visual system of this snail and compared our findings with those reported from other species. At least one serotonin-and one FMRF-amidergic fibre were labeled in each optic nerve, and since no cell bodies in the eye showed immunoreactivity to these neurotransmitters, we believe that efferent fibres with somata located in the central ganglia branch at the base of the eye and probably release 5HT and FMRF-amide as neuro-hormones. Double labelling revealed retrograde transport of neurobiotin through the optic nerve, allowing us to conclude that the central pathways and serotonin-and FMRF-amideimmunoreactive cells and fibres have different locations in the CNS in Lymnaea stagnalis. The chemical nature of the fibres, which connect the two eyes in Lymnaea stagnalis, is neither serotoninergic nor FMRF-amidergic.

Afferent and efferent pathways in the visual system of the freshwater snail Planorbarius corneus

Afferent and efferent neural elements of the retina and central ganglia in the freshwater snail Planorbarius corneus were labelled using retrograde transport of neurobiotin through the optic nerve.Axons of at least some photoreceptor cells become direct contributors to the optic nerve as no synaptic junctions could be detected.The processes enter the cerebral ganglion and form a dense bundle of thin afferent fibres,the so-called optical neuropil.Efferent neurons were revealed in all ganglia,except the buccal ones.Some of the ascending axons branch in the cerebral ganglia,cross the cerebro-cerebral commissure,reach the contralateral eye and form arborizations in the eye cup.Some efferent neurons send axons to different peripheral nerves as well：n.n.intestinalis,pallialis dexter,pallialis sinister internus et externus.Serotonin-and FMRF-amide-ergic fibres were revealed in the optic nerve.These fibres belong to those central neurons which send their axons to the ipsilateral eye only.They form abundant varicoses in the eye cup and nuclear layer of the retina,and possibly help to regulate retinal sensitivity to light.

Cytoplasmic dynein:a key player in neurodegenerative and neurodevelopmental diseases

Cytoplasmic dynein is the most important molecular motor driving the movement of a wide range of cargoes towards the minus ends of microtubules.As a molecular motor protein,dynein performs a variety of basic cellular functions including organelle transport and centrosome assembly.In the nervous system,dynein has been demonstrated to be responsible for axonal retrograde transport.Many studies have revealed direct or indirect evidence of dynein in neurodegenerative diseases such as amyotrophic lateral sclerosis,Charcot-Marie-Tooth disease,Alzheimer’s disease,Parkinson’s disease and Huntington’s disease.Among them,a number of mutant proteins involved in various neurodegenerative diseases interact with dynein.Axonal transport disruption is presented as a common feature occurring in neurodegenerative diseases.Dynein heavy chain mutant mice also show features of neurodegenerative diseases.Moreover,defects of dynein-dependent processes such as autophagy or clearance of aggregation-prone proteins are found in most of these diseases.Lines of evidence have also shown that dynein is associated with neurodevelopmental diseases.In this review,we focus on dynein involvement in different neurological diseases and discuss potential underlying mechanisms.