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Neuroprotection with androgens following partial motoneuron depletion: A role for microglia
Kiley BJ, Sengelaub DR (2015) Neuroprotection with androgens following partial motoneuron depletion: A role for microglia. Neuroscience 2015 Abstracts 689.18/K11. Society for Neuroscience, Chicago IL.
Summary: Neurodegenerative disease or nerve injury results in the loss of spinal motoneurons, and remaining motoneurons show a variety of morphological and functional changes. We have previously demonstrated that partial depletion of motoneurons innervating the quadriceps muscles induces dendritic atrophy in remaining motoneurons, with 70% decreases in dendritic length. Treatment with testosterone is neuroprotective, and dendritic atrophy following partial motoneuron depletion is attenuated. In the present study, we explored a potential mechanism for this induced atrophy and the protection by androgen treatment, examining the response of microglia to the partial depletion of motoneurons with and without testosterone treatment. Microglia are activated locally and recruited from other sites in response to injury. Microglia are involved in the removal of synapses and dendrites after injury, and there is evidence that their activation is influenced by steroid hormones. Motoneurons innervating the vastus medialis muscle in adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, saporin-injected rats were given systemic treatments via interscapular implants containing testosterone or left blank. One or three weeks later, microglia were visualized after immunohistochemical staining for Iba1. Microglia surrounding the injured motoneurons were classified as monitoring or activated (primed, reactive, or ameboid) based on morphology and counted stereologically. Compared with intact males, partial motoneuron depletion resulted in increases in the total number of microglia (78% and 24% at 1 and 3 weeks post-saporin, respectively) in the quadriceps motor pool. These changes were driven by increases in the number of activated microglia compared to levels found in intact animals; the number of activated microglia increased by 144% at 1 week post-saporin, and remained elevated at 3 weeks (51%). The increases in the number of activated microglia were attenuated with testosterone treatment; the number of activated forms increased only 34% and 17% at 1 and 3 weeks post-saporin, respectively. These findings suggest that the dendritic atrophy observed in remaining motoneurons after partial motoneuron depletion could be a result of increased microglial activation in the injury site, resulting in collateral damage through synaptic stripping and dendritic loss. The attenuation of both dendritic atrophy and microglial activation with testosterone treatment supports this potential causal effect, and further supports a role for hormones as neurotherapeutic agents in the injured nervous system.
Related Products: CTB-SAP (Cat. #IT-14)
Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite.
Xing D, Wu Y, Li G, Song S, Liu Y, Liu H, Wang X, Fei Y, Zhang C, Li Y, Zhang L (2015) Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite. Physiol Behav 147:291-299. doi: 10.1016/j.physbeh.2015.04.034
Summary: Sodium concentration in the cerebrospinal fluid (CSF) is tightly regulated, and this regulation requires numerous sensors spread throughout the brain. Here the authors injected 900 ng CTB-SAP (Cat. #IT-14) into the lateral ventricles. Investigation of spontaneous and induced sodium intake indicates the CSF-contacting nucleus is an important link in the sodium sensing network, and interacts with the lateral parabrachial nucleus.
Related Products: CTB-SAP (Cat. #IT-14)
Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections.
Nichols N, Vinit S, Bauernschmidt L, Mitchell G (2015) Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exp Neurol 267:18-29. doi: 10.1016/j.expneurol.2014.11.011
Summary: Amyotrophic lateral sclerosis (ALS) ultimately causes death from ventilator failure. Genetic models of ALS suffer from high variability of the rate, timing, and extent of respiratory motor neuron death. The authors created a novel model of induced respiratory motor neuron death using CTB-SAP (Cat. #IT-14). Rats received 25 μg or 50 μg intrapleural injections of CTB-SAP; Saporin (Cat. #PR-01) was used as a control. After 7 days, motor neuron survival approximated what is seen in end-stage ALS rats, while there was minimal cell death in other brainstem or spinal cord regions. CTB-SAP also caused microglial activation, decreased breathing during chemoreceptor stimulation, and diminished phrenic motor output in anesthetized rats – all hallmarks of ALS.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Novel mechanisms of spinal cord plasticity in a mouse model of motoneuron disease.
Gulino R, Parenti R, Gulisano M (2015) Novel mechanisms of spinal cord plasticity in a mouse model of motoneuron disease. Biomed Res Int 2015:654637. doi: 10.1155/2015/654637
Summary: Here the authors investigate spinal plasticity mechanisms involving a number of different proteins, including BDNF, Shh, Notch-1, Numb, and Noggin. The model used is a mouse motoneuron depletion strategy, where the animals receive 3 μg of CTB-SAP (Cat. #IT-14) into each of the medial and lateral gastrocnemius muscles. The results indicate that TDP-43, a nuclear DNA/RNA binding protein, may be an important regulator of synaptic plasticity.
Related Products: CTB-SAP (Cat. #IT-14)
Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress.
Wu Y, Song S, Liu H, Xing D, Wang X, Fei Y, Li G, Zhang C, Li Y, Zhang L (2015) Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress. Neuropeptides 51:43-54. doi: 10.1016/j.npep.2015.03.007
Summary: The CSF-contacting nucleus (CSF-CN) is a brain structure containing neurons that can bidirectionally transmit signals between the brain parenchyma and the CSF. In order to better understand what regulatory peptides modulate this organ, the authors eliminated the CSF-CN of rats with a 500-ng icv injection of CTB-SAP (Cat. #IT-14). Saporin (Cat. #PR-01) was used as a control. The elimination of the CSF-CN worsened the response to chronic immobilization stress; with other data this information suggests that the CSF-CN uses adrenomedullin as a stress-related peptide.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission.
Liu H, Yan W, Lu X, Zhang X, Wei J, Wang X, Wang T, Wu T, Cao J, Shao C, Zhou F, Zhang H, Zhang P, Zang T, Lu X, Cao J, Ding H, Zhang L (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485. doi: 10.1016/j.expneurol.2014.07.018
Summary: The first synapse in the pain pathway is in the spinal dorsal horn, and several sites are involved in the descending control of pain. Previous studies have suggested that cerebrospinal fluid-contacting neurons may facilitate signal transmission and substance transport between the brain parenchyma and the CSF, including processes that modulate pain transmission. The authors administered CTB-SAP (Cat. #IT-14) into the right lateral ventricle of rats. Saporin (Cat. #PR-01) was used as a control. The results indicate that the 5-HT pathway contacting the CSF is an important piece in the descending inhibitory system controlling spinal transmission of pain.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
[Targeted damage of the cerebrospinal fluid-contacting nucleus contributes to the pain behavior and the expression of 5-HT and c-Fos in spinal dorsal horn of rats].
Cao J, Wu T, Zhang L (2014) [Targeted damage of the cerebrospinal fluid-contacting nucleus contributes to the pain behavior and the expression of 5-HT and c-Fos in spinal dorsal horn of rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 30:218-222.
Summary: Pain threshold, 5-hydroxytryptamine (5-HT) expression, and c-Fos expression were measured in rats after treatment with CTB-SAP (Cat. #IT-14). Use of CTB-SAP reduced the number of neurons in the cerebrospinal fluid (CSF)-contacting nucleus over time until no neurons could be detected by the 10th day post-injection. 5-HT and c-Fos expression in the spinal dorsal horn gradually increased, and was negatively correlated with the pain threshold. The data indicate that neurons in the CSF-contacting nucleus are involved in pain regulation, and that expression of 5-HT and c-Fos is part of this regulatory pathway.
Related Products: CTB-SAP (Cat. #IT-14)
Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord.
Gulino R, Gulisano M (2013) Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord. J Neurol Sci 332(1-2):102-109. doi: 10.1016/j.jns.2013.06.029
Summary: Noggin (NOG) and Sonic hedgehog (Shh) are both involved in the generation and organization of neural tissues. In order to clarify the role of these two proteins in the regulation of neurogenesis and/or neuroplasticity the authors used a motoneuron depletion model in the mouse spinal cord. 3 μg of CTB-SAP (Cat. #IT-14) was injected into each of the medial and lateral gastrocnemius muscles and the expression of NOG and Shh were monitored. Motor performance also correlated with NOG and Shh levels, indicating that these proteins could play roles in regeneration and functional restoration.
Related Products: CTB-SAP (Cat. #IT-14)
Neural plasticity in injured spinal cord.
Gulisano M, Parenti R, Gulino R (2012) Neural plasticity in injured spinal cord. Neuroscience 2012 Abstracts 846.09. Society for Neuroscience, New Orleans, LA.
Summary: Sonic hedgehog and Noggin are morphogenetic factors involved in neural induction and ventralization of the neural tube, but recent findings suggest that they could participate in regeneration and functional recovery after injury. Here, in order to verify if these mechanisms could occur in the spinal cord and involve synaptic plasticity, we measured the expression levels of Sonic hedgehog, Noggin, Choline acetyltransferase, Synapsin-I, and Glutamate receptor subunits (GluR1, GluR2, GluR4), in a motoneuron-depleted mouse spinal lesion model obtained by intramuscular injection of Cholera toxin-B saporin. The lesion caused differential expression changes of the analyzed proteins. Moreover, motor performance was found correlated with Sonic hedgehog and Noggin expression in lesioned animals. The results also suggest that Sonic hedgehog could collaborate in modulating synaptic plasticity. Together, these findings confirm that the injured mammalian spinal cord has intrinsic potential for repair and that some proteins classically involved in development, such as Sonic hedgehog and Noggin could have important roles in regeneration and functional restoration, by mechanisms including synaptic plasticity.
Related Products: CTB-SAP (Cat. #IT-14)
Involvement of brain-derived neurotrophic factor and sonic hedgehog in the spinal cord plasticity after neurotoxic partial removal of lumbar motoneurons.
Gulino R, Gulisano M (2012) Involvement of brain-derived neurotrophic factor and sonic hedgehog in the spinal cord plasticity after neurotoxic partial removal of lumbar motoneurons. Neurosci Res 73(3):238-247. doi: 10.1016/j.neures.2012.04.010
Summary: In this work the authors created a motoneuron depletion with bilateral 6.0-μg injections of CTB-SAP (Cat. #IT-14) into the medial and lateral gastrocnemius muscles of rats. The results indicate BDNF and sonic hedgehog may collaborate in modulating synaptic plasticity after loss of motoneurons.
Related Products: CTB-SAP (Cat. #IT-14)