Transcorneal electrical stimulation reduces neurodegenerative process in a mouse model of glaucoma.
Glaucoma; Optic nerve; BDNF; Retina; p75NTR; Transcorneal electrical stimulation
Glaucoma is a neurodegenerative disease in which the retinal ganglion cell axons of the optic nerve degenerate concomitant with synaptic changes in the retina, leading finally to death of the retinal ganglion cells (RGCs). Electrical stimulation has been used to improve neural regeneration in a variety of systems, including in diseases of the retina. Therefore, the focus of this study was to investigate whether transcorneal electrical stimulation (TES) in the DBA2/J mouse model of glaucoma could improve retinal or optic nerve pathology and serve as a minimally invasive treatment option. Mice (10 months-old) received 21 sessions of TES over 8 weeks, after which we evaluated RGC number, axon number, and anterograde axonal transport using histology and immunohistochemistry. To gain insight into the mechanism of proposed protection, we also evaluated inflammation by quantifying CD3 + T-cells and Iba1 + microglia; perturbations in metabolism were shown via the ratio pAMPK to AMPK, and changes in trophic support were tested using protein capillary electrophoresis. We found that TES resulted in RGC axon protection, a reduction in inflammatory cells and their activation, improved energy homeostasis, and a reduction of the cell death-associated p75NTR. Collectively, the data indicated that TES maintained axons, decreased inflammation, and increased trophic factor support, in the form of receptor presence and energy homeostasis, suggesting that electrical stimulation impacts several facets of the neurodegenerative process in glaucoma.
Jassim, AH;Cavanaugh M;Shah JS;Willits R;Inman DM
Annals Of Biomedical Engineering
2020
2020-09-24
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1007/s10439-020-02608-8" target="_blank" rel="noreferrer noopener">10.1007/s10439-020-02608-8</a>
Reduction In The Number Of Spinal Motor-neurons In Neurotrophin-3-deficient Mice
bdnf; cell-death; cord; expression; fusimotor neurons; motoneurons; motor neurons; muscle spindles; nerve; Neurosciences & Neurology; neurotrophic factor; neurotrophins; proprioception; rat muscle-spindles; size; survival
The effects of a deficiency of neurotrophin-3 on spinal motor neurons were assessed by determining the number of myelinated nerve fibers in lumbar ventral spinal roots of mice with a deletion in the neurotrophin-3 gene. Few or no small-caliber (fusimotor) nerve fibers were present in the L4 ventral root of homozygous mutant mice lacking both copies of the neurotrophin-3 gene, and approximately one-half of the normal complement of the fibers was present in heterozygous mice having one copy of the neurotrophin-3 gene relative to wild type mice at two weeks of age. Numbers of fusimotor nerve fibers paralleled numbers of muscle spindles, the target organs of fusimotor innervation, in hindlimb muscles. Muscle spindles and intrafusal fibers were absent in the soleus muscles of homozygous mutants, and were reduced by approximately 50% in heterozygous relative to wild type mice in accord with previous reports. Neurotrophin-3 might be generated by the intrafusal fibers and may provide a target-derived neurotrophic support for developing fusimotor neurons because in the absence of muscle spindles the neurons did not differentiate and/or survive. In contrast, a great majority of skeletomotor neurons that innervate extrafusal muscle fibers differentiated normally in the absence of neurotrophin-3. This study, analysed in conjunction with our previously reported data, suggests that neurotrophin-3 acts in a coordinated fashion to support, either directly or indirectly, the development of each of the three classes of cells-Ia and Ib sensory neurons, fusimotor neurons, and intrafusal muscle fibers-that comprise the limb proprioceptive system.
Kucera J; Ernfors P; Walro J; Jaenisch R
Neuroscience
1995
1995-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0306-4522(95)00221-4" target="_blank" rel="noreferrer noopener">10.1016/0306-4522(95)00221-4</a>
Developmental pyrethroid exposure causes long-term decreases of neuronal sodium channel expression.
Animals; BDNF; Brain-Derived Neurotrophic Factor/metabolism; Cerebral Cortex/*drug effects/growth & development/metabolism; Corpus Striatum/*drug effects/growth & development/metabolism; Deltamethrin; Female; Inbred C57BL; Insecticides/*toxicity; Male; Messenger/metabolism; Mice; Neurodevelopmental; Neurons/*drug effects/metabolism; Nitriles/*toxicity; Pregnancy; Prenatal Exposure Delayed Effects/*metabolism; Pyrethrins/*toxicity; Pyrethroid; RNA; Sodium channel; Voltage-Gated Sodium Channels/*metabolism
Pyrethroid insecticide use has increased over recent years because of their low to moderate acute toxicity in mammals. However, there is increasing concern over the potential detrimental effects of pyrethroids on developing animals. Most recently, we have shown that developmental exposure to deltamethrin results in long-term neurobehavioral effects. Pyrethroids exert their toxicity by acting on the voltage-gated sodium channel (Nav), delaying channel inactivation and causing hyperexcitability in the nervous system. Previous in vitro studies found that exposure to agents that increase Na(+) influx, including deltamethrin decreased Nav mRNA expression. However, it is unknown whether this occurs in vivo. To determine whether developmental pyrethroid exposure decreases Nav mRNA expression, pregnant mice were exposed to the pyrethroid deltamethrin (0 or 3mg/kg) every three days throughout gestation and lactation. Nav mRNA expression was measured in the striatum and cortex of the offspring at 10-11 months of age, a time at which behavioral abnormalities were still observed. Developmental exposure to deltamethrin decreased expression of Nav mRNA in a region- and isoform-specific fashion by 24-50%. Deltamethrin exposure also resulted in the persistent down-regulation of brain-derived neurotrophic factor (Bdnf) in the striatum by 66% but not in the cortex, suggesting a plausible mechanism for some of the associated behavioral effects observed previously. Taken together these data suggest that developmental deltamethrin exposure results in persistent deficits in Nav and BDNF mRNA expression that may contribute to long-term behavioral deficits.
Magby Jason P; Richardson Jason R
Neurotoxicology
2017
2017-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuro.2016.04.002" target="_blank" rel="noreferrer noopener">10.1016/j.neuro.2016.04.002</a>