[Neonatal hypoxia-ischemia: cellular and molecular brain damage and therapeutic modulation of neurogenesis].

 

 

Image result for Rev Neurol journal

“Perinatal asphyxia remains a major cause of both mortality and neurological morbidity. Neonatal encephalopathy affects to 1-3/1,000 newborns, leading to significant brain damage and childhood disability.

The only standard therapy is moderate hypothermia, whose efficacy, despite proved, is limited, being partially effective.

The use of therapeutic agents such as erythropoietin and cannabinoids and mesenchymal stem cells have shown promising results in experimental models of perinatal asphyxia, being able of modulate neurogenesis, neuronal plasticity and neuroreparation processes after hypoxic-ischemic brain injury.”

https://www.ncbi.nlm.nih.gov/pubmed/30560986

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoids as Regulators of Neural Development and Adult Neurogenesis

“Neurogenesis plays an indispensable role in the formation of the nervous system during development. The discovery that the adult brain still maintains neurogenic niches that allow the continued production of new cells after birth has changed the field of neuroscience. It has also opened a new venue of opportunities for the treatment of central nervous system disorders related to neuronal loss. This chapter has reviewed the studies showing that genetic or pharmacological manipulation of cannabinoid receptors (CB1 and CB2) or the enzymes responsible for endocannabinoid metabolism modify/regulate cell proliferation and neurogenesis during development and in the adult brain. A better characterization of the mechanisms involved in these effects could contribute to the development of new therapeutic alternatives to neurodegenerative and psychiatric disorders.”

https://link.springer.com/chapter/10.1007/978-3-319-49343-5_6?fbclid=IwAR1yxGqvrq_9Zva3HLEqjh2WrNRTxPN6Hy_IO8l2IN8v9BCNBG2jDks9N1w

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation.

Brain, Behavior, and Immunity

“New neurons are continuously produced by neural stem cells (NSCs) within the adult hippocampus. Numerous diseases, including major depressive disorder and HIV-1 associated neurocognitive disorder, are associated with decreased rates of adult neurogenesis. A hallmark of these conditions is a chronic release of neuroinflammatory mediators by activated resident glia.

Recent studies have shown a neuroprotective role on NSCs of cannabinoid receptor activation. Yet, little is known about the effects of GPR55, a candidate cannabinoid receptor, activation on reductions of neurogenesis in response to inflammatory insult.

In the present study, we examined NSCs exposed to IL-1β in vitro to assess inflammation-caused effects on NSC differentiation and the ability of GPR55 agonists to attenuate NSC injury.

Taken together, these results suggest a neuroprotective role of GPR55 activation on NSCs in vitro and in vivo and that GPR55 provides a novel therapeutic target against negative regulation of hippocampal neurogenesis by inflammatory insult.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus.

Cerebral Cortex

“Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive.

NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1).

To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice.

These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30307491

https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhy258/5126794

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

[Should ophtalmologists recommend medical cannabis to patients with glaucoma?]

 Image result for ugeskr laeger

“Cannabis has been widely used for various medical purposes since before year 2000 BC. Its effects are mediated by cannabinoids and stimulation of mainly G-protein coupled cannabinoid receptors.

In 1971, subjects who smoked marihuana, showed a decrease in the intraocular pressure.

Later investigations additionally revealed a neuroprotective effect of both ∆-9-tetrahydrocannabinol and cannabidiol (CBD).

Furthermore, CBD was found to promote neurogenesis. The aim of this review is to provide an overview of the potential use of cannabinoids in the treatment of glaucoma.”

https://www.ncbi.nlm.nih.gov/pubmed/30020072

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Modulation of the Cannabinoid System: A New Perspective for the Treatment of the Alzheimer’s Disease.

“The pathogenesis of Alzheimer’s disease (AD) is somewhat complex and has yet to be fully understood. As the effectiveness of the therapy currently available for AD has proved to be limited, the need for new drugs has become increasingly urgent.

The modulation of the endogenous cannabinoid system (ECBS) is one of the potential therapeutic approaches that is attracting a growing amount of interest. The ECBS consists of endogenous compounds and receptors. The receptors CB1 and CB2 have already been well characterized: CB1 receptors, which are abundant in the brain, particularly in the hippocampus, basal ganglia and cerebellum, regulate memory function and cognition.

It has been suggested that the activation of CB1 receptors reduces intracellular Ca concentrations, inhibits glutamate release and enhances neurotrophin expression and neurogenesis. CB2 receptors are expressed, though to a lesser extent, in the central nervous system, particularly in microglia and in immune system cells involved in the release of cytokines. CB2 receptors have been shown to be upregulated in neuritic plaque-associated migroglia in the hippocampus and entorhinal cortex of patients, which suggests that these receptors play a role in the inflammatory pathology of AD.

The role of the ECBS in AD is supported by cellular and animal models. By contrast, few clinical studies designed to investigate therapies aimed at reducing behaviour disturbances, especially night-time agitation, eating behaviour and aggressiveness, have yielded positive results. In this review, we will describe how the manipulation of the ECBS offers a potential approach to the treatment of AD.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Brain endocannabinoid signaling exhibits remarkable complexity.

Image result for Brain Res Bull.

“The endocannabinoid (eCB) signaling system is one of the most extensive of the mammalian brain. Despite the involvement of only few specific ligands and receptors, the system encompasses a vast diversity of triggered mechanisms and driven effects. It mediates a wide range of phenomena, including the regulation of transmitter release, neural excitability, synaptic plasticity, impulse spread, long-term neuronal potentiation, neurogenesis, cell death, lineage segregation, cell migration, inflammation, oxidative stress, nociception and the sleep cycle. It is also known to be involved in the processes of learning and memory formation. This extensive scope of action is attained by combining numerous variables. In a properly functioning brain, the correlations of these variables are kept in a strictly controlled balance; however, this balance is disrupted in many pathological conditions. However, while this balance is known to be disrupted by drugs in the case of addicts, the stimuli and mechanisms influencing the neurodegenerating brain remain elusive. This review examines the multiple factors and phenomena affecting the eCB signaling system in the brain. It evaluates techniques of controlling the eCB system to identify the obstacles in their applications and highlights the crucial interdependent variables that may influence biomedical research outcomes.”

https://www.ncbi.nlm.nih.gov/pubmed/29953913

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis

British Journal of Pharmacology banner

“The cannabinoid system exerts functional regulation of neural stem cell (NSC) proliferation and adult neurogenesis, yet not all effects of cannabinoid-like compounds seen can be attributed to the cannabinoid 1 receptor (CB1 R) or cannabinoid 2 receptor (CB2 R).

The recently de-orphaned GPR55 has been shown to be activated by numerous cannabinoid ligands suggesting that GPR55 is a third cannabinoid receptor.

Here we examined the role of GPR55 activation in NSC proliferation and early adult neurogenesis.

CONCLUSIONS AND IMPLICATIONS:

Together, these findings suggest GPR55 activation as a novel target and strategy to regulate NSC proliferation and adult neurogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/29888782

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14387

“The orphan receptor GPR55 is a novel cannabinoid receptor”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoid signalling in embryonic and adult neurogenesis: possible implications for psychiatric and neurological disorders.

 Image result for acta neuropsychiatrica

“Cannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods.

The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions.

An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29764526

https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/cannabinoid-signalling-in-embryonic-and-adult-neurogenesis-possible-implications-for-psychiatric-and-neurological-disorders/E9DE9116DC604D976C9C7B0D2D254674

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Biphasic Effects of THC in Memory and Cognition.

Publication cover image

“A generally undesired effect of cannabis smoking is a reversible disruption of short term memory induced by delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis.

However, this paradigm has been recently challenged by a group of scientists who have shown that THC is also able to improve neurological function in old animals when chronically administered at low concentrations.

Moreover, recent studies demonstrated that THC paradoxically promotes hippocampal neurogenesis, prevents neurodegenerative process occurring in Alzheimer Disease, protects from inflammation-induced cognitive damage and restores memory and cognitive function in old mice.

With the aim to reconcile these seemingly contradictory facts, the present work will show that such paradox can be explained within the framework of hormesis, defined as biphasic dose responses. ”

https://www.ncbi.nlm.nih.gov/pubmed/29574698

https://onlinelibrary.wiley.com/doi/abs/10.1111/eci.12920

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous