“The main pathological feature of Parkinson’s disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus. The mRNA expression analysis further demonstrated that AM1241 increased expression of the CB2R and activated Parkin/PINK1 signaling pathways. Furthermore, the increased number of TH-positive cells in the substantia nigra indicated that AM1241 regenerated DA neurons in PD mice, and could therefore be a potential candidate for PD treatment. The clear co-localization of CB2R and DA neurons suggested that AM1241 targeted CB2R, thus also identifying a novel target for PD treatment. In conclusion, the selective CB2 agonist AM1241 has a significant therapeutic effect on PD mice and resulted in regeneration of DA neurons following MPTP-induced neurotoxicity. The possible mechanisms underlying the neurogenesis effect of AM1241 might be the induction of CB2R expression and an increase in phosphorylation of the PI3K/AKT signaling pathway.”
Tag Archives: neurogenesis
Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders.
“Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.”
https://www.ncbi.nlm.nih.gov/pubmed/28588483
http://journal.frontiersin.org/article/10.3389/fphar.2017.00269/full
Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogen-activated protein kinase activation.
“The endocannabinoid system regulates neurite outgrowth and neurogenesis during development of the central nervous system. Cannabinoid receptor 1 (CB1R) is expressed in neurons, including the somata and fibers, that innervate the endometrial ectopic cyst in rats. This finding may provide a new therapeutic target for patients with endometriosis.” https://www.ncbi.nlm.nih.gov/pubmed/28322749]]>
Regulation of Adult Neurogenesis by Cannabinoids
“In the adult mammalian brain, new neurons are born throughout life, and these new cells may influence learning, memory, olfaction, and even mood. The putative function of these new neurons suggests that manipulation of adult neurogenesis could be used therapeutically in the future, and emphasizes the importance of understanding how neurogenesis is regulated. Voluntary exercise and antidepressants are examples of factors that increase neurogenesis, while stress and drugs of abuse – alcohol, nicotine, psychostimulants, opiates – decrease neurogenesis. In contrast to the clear negative influence of these drugs of abuse, cannabinoids have mixed influence, with some marijuana-like compounds actually enhancing neurogenesis.” https://www.researchgate.net/publication/264424221_Regulation_of_Adult_Neurogenesis_by_Cannabinoids
“The role of cannabinoids in adult neurogenesis” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543605/
“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects” http://www.jci.org/articles/view/25509
]]>In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease.
“Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress.
Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics.
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD.
Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD.
The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis.
Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models.
Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.
The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28217094
“It is unlikely that any drug acting on a single pathway or target will mitigate the complex pathoetiological cascade leading to AD. Therefore, a multifunctional drug approach targeting a number of AD pathologies simultaneously will provide better, wider-ranging benefits than current therapeutic approaches. Importantly, the endocannabinoid system has recently gained attention in AD research as it is associated with regulating a variety of processes related to AD, including oxidative stress, glial cell activation and clearance of macromolecules. The phytocannabinoid cannabidiol (CBD) is a prime candidate for this new treatment strategy. CBD has been found in vitro to be neuroprotective, to prevent hippocampal and cortical neurodegeneration, to have anti-inflammatory and antioxidant properties, reduce tau hyperphosphorylation and to regulate microglial cell migration. Furthermore, CBD was shown to protect against Aβ mediated neurotoxicity and microglial-activated neurotoxicity, to reduce Aβ production by inducing APP ubiquination and to improve cell viability,. These properties suggest that CBD is perfectly placed to treat a number of pathologies typically found in AD. The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies.” http://journal.frontiersin.org/article/10.3389/fphar.2017.00020/full
In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease.
“Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress.
Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics.
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD.
Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD.
The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis.
Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models.
Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.
The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28217094
“It is unlikely that any drug acting on a single pathway or target will mitigate the complex pathoetiological cascade leading to AD. Therefore, a multifunctional drug approach targeting a number of AD pathologies simultaneously will provide better, wider-ranging benefits than current therapeutic approaches. Importantly, the endocannabinoid system has recently gained attention in AD research as it is associated with regulating a variety of processes related to AD, including oxidative stress, glial cell activation and clearance of macromolecules. The phytocannabinoid cannabidiol (CBD) is a prime candidate for this new treatment strategy. CBD has been found in vitro to be neuroprotective, to prevent hippocampal and cortical neurodegeneration, to have anti-inflammatory and antioxidant properties, reduce tau hyperphosphorylation and to regulate microglial cell migration. Furthermore, CBD was shown to protect against Aβ mediated neurotoxicity and microglial-activated neurotoxicity, to reduce Aβ production by inducing APP ubiquination and to improve cell viability,. These properties suggest that CBD is perfectly placed to treat a number of pathologies typically found in AD. The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies.” http://journal.frontiersin.org/article/10.3389/fphar.2017.00020/full
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“As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically.
Moreover, recent studies have shown that endogenous 
