Cognitive decline due to strokes, Alzheimer’s disease, brain cancer and chemotherapy, and many other neurodegenerative diseases is generally irreversible or has limited treatment options. On September 10th 2019, Dr. Meharvan Singh, the Vice Dean of Research and a professor in the Department of Cellular and Molecular Physiology at Loyola University Chicago Stritch School of Medicine, gave a presentation on his ongoing research regarding the neurobiology of hormones and their implications for aging, cognitive decline due to glioblastomas and chemotherapy and neurodegenerative diseases. Dr. Singh et al.’s publication, “Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia,” examines the interaction among the following: a specific hormone (progesterone or P4), the neurotrophin called brain-derived neurotrophic factor (BDNF), a microRNA called let-7i, and a membrane-associated progesterone receptor called Pgrmc1.
Progesterone has been observed to exhibit neuroprotective effects in mice models with the neuropathology of an ischemic stroke. This discovery has significant implications as progesterone has shown potential in preventing the progression of the neurodegenerative metabolic events caused by an ischemic stroke and has even shown to reduce the stroke damage. In another of Dr. Singh’s studies, Dr. Singh et al., found that progesterone “elicits the release of BDNF via…Pgmc1.” Typically, BDNF functions to promote neuronal growth, maturation, and the formation of synapses between neurons in a process called synaptogenesis. In previous research, synaptogenesis in a specific brain region, the penumbra, has shown to enhance functional recovery following a stroke. BDNF is also known to be critical mediator of progesterone’s protective effects and progesterone has been. Thus, progesterone triggers the release of BDNF from the receptor, Pmgrc1, allowing for the neuroprotective effects to take hold.
Following a stroke, the brain’s pathophysiology reflects an increased expression of the microRNA, let-7i. This let-7i overexpression is associated with decrease levels of the membrane-associated progesterone receptor, Pgrmc1. As a result of the decreased levels of Pgrmc1, there are lower levels of BDNF, and thus less protective effects taking place. Dr. Singh et al.’s findings show that introducing an inhibitory factor that suppresses let-7i as well as introducing progesterone leads to higher levels of Pgrmc1 and BDNF, providing an effective treatment for strokes. When this treatment was introduced in the experimental mouse model, the mice exhibited complete motor function recovery.
These findings are incredibly important in the study of therapies and treatments for many neurodegenerative diseases as many recent publications are increasingly showing a multitude of neurodegenerative diseases being influenced by BDNF levels. Parkinson’s disease is characterized by gradual cell death of dopamine-producing neurons, resulting in symptoms such as the loss of control over movements, slurred speech, impaired posture and balance, tremors, muscle rigidity and so on. The news article, “Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests,” reports the findings of a study in which more severe Parkinson’s disease-related cognitive impairment is associated with ineffective BDNF genes. Due to a mutation of one amino acid within the BDNF gene, the gene is unable to code for the crucial BDNF proteins. Those with multiple copies of the BDNF gene were much more likely to develop cognitive decline than those with the same amount of non-mutated BDNF gene.
In relation to Dr. Singh’s research, we might consider how introducing progesterone as a therapy may affect the pathophysiology of Parkinson’s. Furthermore, researchers might consider the let-7i levels when further examining the pathophysiology of Parkinson’s and compare it to that of ischemic stroke pathophysiology. BDNF provides a link between seemingly incurable neurodegenerative diseases. Further investigation into BDNF, its associated cell signaling and mediators may provide more therapies and treatments to restore function and possibly reverse cognitive impairment.
Dr Singh’s Research:
Nguyen, T., Su, C., & Singh M. (2018) “Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia.” Proceedings o the National Academy of Sciences, 115(41), doi: 10.1073/pnas.1803384115.Neurodegenerative Disease and BDNF
BDNF and Parkinson’s Article:
Silva, Catarina. “Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests.” Parkinson’s News Today, 21 May 2019, https://parkinsonsnewstoday.com/2019/05/21/cognitive-impairment-parkinsons-linked-bdnf-mutation/.
Progesterone has been observed to exhibit neuroprotective effects in mice models with the neuropathology of an ischemic stroke. This discovery has significant implications as progesterone has shown potential in preventing the progression of the neurodegenerative metabolic events caused by an ischemic stroke and has even shown to reduce the stroke damage. In another of Dr. Singh’s studies, Dr. Singh et al., found that progesterone “elicits the release of BDNF via…Pgmc1.” Typically, BDNF functions to promote neuronal growth, maturation, and the formation of synapses between neurons in a process called synaptogenesis. In previous research, synaptogenesis in a specific brain region, the penumbra, has shown to enhance functional recovery following a stroke. BDNF is also known to be critical mediator of progesterone’s protective effects and progesterone has been. Thus, progesterone triggers the release of BDNF from the receptor, Pmgrc1, allowing for the neuroprotective effects to take hold.
Following a stroke, the brain’s pathophysiology reflects an increased expression of the microRNA, let-7i. This let-7i overexpression is associated with decrease levels of the membrane-associated progesterone receptor, Pgrmc1. As a result of the decreased levels of Pgrmc1, there are lower levels of BDNF, and thus less protective effects taking place. Dr. Singh et al.’s findings show that introducing an inhibitory factor that suppresses let-7i as well as introducing progesterone leads to higher levels of Pgrmc1 and BDNF, providing an effective treatment for strokes. When this treatment was introduced in the experimental mouse model, the mice exhibited complete motor function recovery.
These findings are incredibly important in the study of therapies and treatments for many neurodegenerative diseases as many recent publications are increasingly showing a multitude of neurodegenerative diseases being influenced by BDNF levels. Parkinson’s disease is characterized by gradual cell death of dopamine-producing neurons, resulting in symptoms such as the loss of control over movements, slurred speech, impaired posture and balance, tremors, muscle rigidity and so on. The news article, “Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests,” reports the findings of a study in which more severe Parkinson’s disease-related cognitive impairment is associated with ineffective BDNF genes. Due to a mutation of one amino acid within the BDNF gene, the gene is unable to code for the crucial BDNF proteins. Those with multiple copies of the BDNF gene were much more likely to develop cognitive decline than those with the same amount of non-mutated BDNF gene.
In relation to Dr. Singh’s research, we might consider how introducing progesterone as a therapy may affect the pathophysiology of Parkinson’s. Furthermore, researchers might consider the let-7i levels when further examining the pathophysiology of Parkinson’s and compare it to that of ischemic stroke pathophysiology. BDNF provides a link between seemingly incurable neurodegenerative diseases. Further investigation into BDNF, its associated cell signaling and mediators may provide more therapies and treatments to restore function and possibly reverse cognitive impairment.
Dr Singh’s Research:
Nguyen, T., Su, C., & Singh M. (2018) “Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia.” Proceedings o the National Academy of Sciences, 115(41), doi: 10.1073/pnas.1803384115.Neurodegenerative Disease and BDNF
BDNF and Parkinson’s Article:
Silva, Catarina. “Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests.” Parkinson’s News Today, 21 May 2019, https://parkinsonsnewstoday.com/2019/05/21/cognitive-impairment-parkinsons-linked-bdnf-mutation/.
No comments:
Post a Comment