The Polarised Life of the Endocannabinoid System in CNS Development

Anavi‐Goffer, Sharon; Mulder, Jan

doi:10.1002/cbic.200800827

Cited by 37 publications

(29 citation statements)

References 144 publications

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“…Late postnatal CPF also inhibits the endocannabinoid metabolizing enzymes FAAH and MAGL and increases endocannabinoid levels in the brain (Carr and others 2013; Carr and others 2011; Carr and others 2014). Since the endocannabinoid signaling is involved in central nervous system functions such as modulation of mood, learning and memory, neurogenesis, cell differentiation, cell migration, neuronal specification and synaptogenesis (Anavi-Goffer and Mulder 2009; Younts and Castillo 2014), more studies investigating CPF-mediated interference in this system during this and other periods of development are warranted. Some deleterious effects are smaller in magnitude when compared to earlier periods of exposure.…”

Section: Organophosphates (Ops)mentioning

confidence: 99%

Developmental neurotoxicity of succeeding generations of insecticides

Abreu‐Villaça

Levin

2017

Environment International

135

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Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk.

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Section: Organophosphates (Ops)mentioning

confidence: 99%

Developmental neurotoxicity of succeeding generations of insecticides

Abreu‐Villaça

Levin

2017

Environment International

135

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“…The endocannabinoid system consists of a group of neuromodulatory lipids that are involved in a variety of physiological processes including appetite, motor learning, synaptic plasticity, and pain sensation. They also play a pivotal role in normal brain development (for reviews see Harkany et al, 2008; Anavi-Goffer and Mulder, 2009). The two main endocannabinoids, arachidonoylethanolamide (AEA or anandamide) and 2-arachidonoylglycerol (2-AG) (Figure 1), are not stored in vesicles due to their lipophilic nature but are synthesized and released on demand in response to elevations in intracellular calcium (Devane at el., 1992; Di Marzo et al, 1994; Mechoulam et al, 1995; Sugiura et al, 1995; Stella et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Low level chlorpyrifos exposure increases anandamide accumulation in juvenile rat brain in the absence of brain cholinesterase inhibition

et al. 2014

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The prevailing dogma is that chlorpyrifos (CPF) mediates its toxicity through inhibition of cholinesterase (ChE). However, in recent years, the toxicological effects of developmental CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We hypothesize that the endocannabinoid system may be an important target because of its vital role in nervous system development. We have previously reported that repeated exposure to CPF results in greater inhibition of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide (AEA), than inhibition of either forebrain ChE or monoacylglycerol lipase (MAGL), the enzyme that metabolizes the endocannabinoid 2-arachidonylglycerol (2-AG). This exposure resulted in the accumulation of 2-AG and AEA in the forebrain of juvenile rats; however, even at the lowest dosage level used (1.0 mg/kg), forebrain ChE inhibition was still present. Thus, it is not clear if FAAH activity would be inhibited at dosage levels that do not inhibit ChE. To determine this, 10 day old rat pups were exposed daily for 7 days to either corn oil or 0.5 mg/kg CPF by oral gavage. At 4 and 12 h post-exposure on the last day of administration, the activities of serum ChE and carboxylesterase (CES) and forebrain ChE, MAGL, and FAAH were determined as well as the forebrain AEA and 2-AG levels. Significant inhibition of serum ChE and CES was present at both 4 and 12 h. There was no significant inhibition of the activities of forebrain ChE or MAGL and no significant change in the amount of 2-AG at either time point. On the other hand, while no statistically significant effects were observed at 4 h, FAAH activity was significantly inhibited at 12 h resulting in a significant accumulation of AEA. Although it is not clear if this level of accumulation impacts brain maturation, this study demonstrates that developmental CPF exposure at a level that does not inhibit brain ChE can alter components of endocannabinoid signaling.

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“…Important neuromaturational processes such as synaptic refinement and myelination occur during adolescent years and continue into young adulthood [2]. In light of ongoing structural brain changes as well as concurrent developments in the endogenous cannabinoid system [3, 4], the potential for neurobehavioral consequences of teenage marijuana use is of great interest.…”

Section: Introductionmentioning

confidence: 99%

Gender effects on amygdala morphometry in adolescent marijuana users

McQueeny

Padula

Price

et al. 2011

Behavioural Brain Research

130

150

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Adolescent developments in limbic structures and the endogenous cannabinoid system suggest that teenagers may be more vulnerable to the negative consequences of marijuana use. This study examined the relationships between amygdala volume and internalizing symptoms in teenaged chronic marijuana users. Participants were 35 marijuana users and 47 controls ages 16–19 years. Exclusions included psychiatric (e.g., mood and anxiety) or neurologic disorders. Substance use, internalizing (anxiety/depression) symptoms and brain scans were collected after 28 days of monitored abstinence. Reliable raters manually traced amygdala and intracranial volumes on high-resolution magnetic resonance images. Female marijuana users had larger right amygdala volumes and more internalizing symptoms than female controls, after covarying head size, alcohol, nicotine and other substance use (p<0.05), while male users had similar volumes as male controls. For female controls and males, worse mood/anxiety was linked to smaller right amygdala volume (p<0.05), whereas more internalizing problems was associated with bigger right amygdala in female marijuana users. Gender interactions may reflect marijuana-related interruptions to sex-specific neuromaturational processes and staging. Subtle amygdala development abnormalities may underlie particular vulnerabilities to sub-diagnostic depression and anxiety in teenage female marijuana users.

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The Polarised Life of the Endocannabinoid System in CNS Development

Cited by 37 publications

References 144 publications

Developmental neurotoxicity of succeeding generations of insecticides

Developmental neurotoxicity of succeeding generations of insecticides

Low level chlorpyrifos exposure increases anandamide accumulation in juvenile rat brain in the absence of brain cholinesterase inhibition

Gender effects on amygdala morphometry in adolescent marijuana users

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