Contributions
Abstract: P1607
Type: LB Poster
Abstract Category: Late Breaking News
The sonic-hedgehog signalling (Shh) pathway has a fundamental role in the development of the central nervous system (CNS). Shh activation has been shown to be important in many CNS post-injury models including stroke and trauma. However, its fundamental role in neuron survival, tissue repair and regeneration is not fully understood. Here, we report the effect of a molecule called smoothened Agonist (SAG) which activates the Shh-Smo signalling - a pathway thought to control proliferation of neuronal progenitors and reactivity of astrocytes, on an in vivo model of demyelination.
Remyelination is an endogenous repair mechanism, characterised by the formation of new myelin sheaths on demyelinated axons. This process is conducted by oligodendrocyte progenitor cells (OPCs) found throughout the CNS. OPCs are activated in response to injury. They proliferate and migrate to the site of the injury, differentiating into mature oligodendrocytes. Remyelination helps with the rapid propagation of nerve impulses along the axon in addition to proving trophic support. Multiple sclerosis(MS) is an example of immune-mediated demyelination in human beings, where remyelination fails, making axons prone to degeneration.
Here, a toxin-induced model of demyelination consisting of bilateral injections of ethidium bromide(EB) into the caudal cerebellar peduncles (CCPs) of female adult rats was used. Animals in the treatment group were given an intraperitoneal injection of SAG.
This project tests the hypothesis that SAG promotes remyelination. In particular, we looked at the effect of SAG on the underlying regenerative and inflammatory processes post injury. We analysed OPC differentiation & proliferation and the infiltration of inflammatory cells into the lesion area using immunohistochemistry.
There was significantly greater differentiation of OPCs into more mature cells (CC1+/Olig2+) in SAG treated animals compared to the control group (p< 0.05).
The inflammatory response assessed by activated macrophages (IBA1+) and reactive astrocytes(GFAP+) was less in SAG treated animals.
In addition, the average lesion area was significantly lower in the treatment group compared to control.
Our results thus far suggest a role for SAG in promoting OPC differentiation and reducing inflammation. This advocates a potential for SAG as an intervention in promoting remyelination which constitutes one of the most important strategies to reduce the detrimental consequences of MS.
Disclosure: Srikirti Kodali: nothing to disclose, Ginez Gonzalez: Nothing to disclose, Vien Nguyen: nothing to disclose, Fernando Gonzalez: nothing to disclose, Prof Robin Franklin: nothing to disclose, Prof David Rowitch: nothing to disclose.
Source of funding:
- Action medical response, registered charity, UK
- Multiple sclerosis society UK
Abstract: P1607
Type: LB Poster
Abstract Category: Late Breaking News
The sonic-hedgehog signalling (Shh) pathway has a fundamental role in the development of the central nervous system (CNS). Shh activation has been shown to be important in many CNS post-injury models including stroke and trauma. However, its fundamental role in neuron survival, tissue repair and regeneration is not fully understood. Here, we report the effect of a molecule called smoothened Agonist (SAG) which activates the Shh-Smo signalling - a pathway thought to control proliferation of neuronal progenitors and reactivity of astrocytes, on an in vivo model of demyelination.
Remyelination is an endogenous repair mechanism, characterised by the formation of new myelin sheaths on demyelinated axons. This process is conducted by oligodendrocyte progenitor cells (OPCs) found throughout the CNS. OPCs are activated in response to injury. They proliferate and migrate to the site of the injury, differentiating into mature oligodendrocytes. Remyelination helps with the rapid propagation of nerve impulses along the axon in addition to proving trophic support. Multiple sclerosis(MS) is an example of immune-mediated demyelination in human beings, where remyelination fails, making axons prone to degeneration.
Here, a toxin-induced model of demyelination consisting of bilateral injections of ethidium bromide(EB) into the caudal cerebellar peduncles (CCPs) of female adult rats was used. Animals in the treatment group were given an intraperitoneal injection of SAG.
This project tests the hypothesis that SAG promotes remyelination. In particular, we looked at the effect of SAG on the underlying regenerative and inflammatory processes post injury. We analysed OPC differentiation & proliferation and the infiltration of inflammatory cells into the lesion area using immunohistochemistry.
There was significantly greater differentiation of OPCs into more mature cells (CC1+/Olig2+) in SAG treated animals compared to the control group (p< 0.05).
The inflammatory response assessed by activated macrophages (IBA1+) and reactive astrocytes(GFAP+) was less in SAG treated animals.
In addition, the average lesion area was significantly lower in the treatment group compared to control.
Our results thus far suggest a role for SAG in promoting OPC differentiation and reducing inflammation. This advocates a potential for SAG as an intervention in promoting remyelination which constitutes one of the most important strategies to reduce the detrimental consequences of MS.
Disclosure: Srikirti Kodali: nothing to disclose, Ginez Gonzalez: Nothing to disclose, Vien Nguyen: nothing to disclose, Fernando Gonzalez: nothing to disclose, Prof Robin Franklin: nothing to disclose, Prof David Rowitch: nothing to disclose.
Source of funding:
- Action medical response, registered charity, UK
- Multiple sclerosis society UK