Peripheral effects of FAAH deficiency on fuel and energy homeostasis: role of dysregulated lysine acetylation.

Background: FAAH (fatty acid amide hydrolase), primarily expressed in the liver, hydrolyzes the endocannabinoids fatty acid ethanolamides (FAA). Human FAAH gene mutations are associated with increased body weight and obesity. In our present study, using targeted metabolite and lipid profiling, and new global acetylome profiling methodologies, we examined the role of the liver on fuel and energy homeostasis in whole body FAAH(-/-) mice.

Ultrastructural analysis of the glutamatergic system in the outer plexiform layer of zebrafish retina.

L-Glutamate, the photoreceptor neurotransmitter, depolarizes horizontal cells and OFF-bipolar cells by ionotropic receptors and hyperpolarizes ON-bipolar cells by metabotropic receptors. Despite extensive light microscopy on the distribution of glutamate receptors in zebrafish retina, there are little ultrastructural data. Given the importance of zebrafish in studies on the genetic manipulation of retinal development and function, precise data on the synaptic neurochemical organization of the zebrafish retina is needed.

Endocannabinoids in the retina: from marijuana to neuroprotection.

The active component of the marijuana plant Cannabis sativa, Delta9-tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic receptors that are distributed throughout the nervous and peripheral organ systems.

Novel processes invaginate the pre-synaptic terminal of retinal bipolar cells.

Mixed-rod cone bipolar (Mb) cells of goldfish retina have large synaptic terminals (10 microm in diameter) that make 60-90 ribbon synapses mostly onto amacrine cells and rarely onto ganglion cells and, in return, receive 300-400 synapses from gamma-aminobutyric acid (GABA)-ergic amacrine cells. Tissue viewed by electron microscopy revealed the presence of double-membrane-bound processes deep within Mb terminals. No membrane specializations were apparent on these invaginating processes, although rare vesicular fusion was observed.

Vanilloid receptor 1 (TRPV1/VR1) co-localizes with fatty acid amide hydrolase (FAAH) in retinal amacrine cells.

Fatty acid amide hydrolase (FAAH) is the degradative enzyme for anandamide (AEA), an endogenous ligand for the vanilloid receptor (TRPV1) and cannabinoid receptor 1. As FAAH and TRPV1 are integral membrane proteins, FAAH activity could modulate the availability of AEA for TRPV1 activation. Previous studies in this laboratory reported an extensive endocannabinoid system in goldfish retina.

Retrograde endocannabinoid inhibition of goldfish retinal cones is mediated by 2-arachidonoyl glycerol.

A functional role for retinal endocannabinoids has not been determined. We characterized retrograde suppression of membrane currents of goldfish cones in a retinal slice. Whole-cell recordings were obtained from cone inner segments under voltage clamp.

Diurnal changes in exocytosis and the number of synaptic ribbons at active zones of an ON-type bipolar cell terminal.

The number and morphology of synaptic ribbons at photoreceptor and bipolar cell terminals has been reported to change on a circadian cycle. Here we sought to determine whether this phenomenon exists at goldfish Mb-type bipolar cell terminals with the aim of exploring the role of ribbons in transmitter release. We examined the physiology and ultrastructure of this terminal around two time points: midday and midnight.

Cannabinoid agonist WIN 55212-2 speeds up the cone response to light offset in goldfish retina.

Goldfish cones contain CB1 receptors at the synaptic terminal, selectively accumulate 3H-anandamide, and contain fatty acid amide hydrolase-immunoreactivity, and voltage-gated calcium and potassium currents are modulated by CB1 ligands (Yazulla et al., 2000; Fan & Yazulla, 2003; Glaser et al., 2005).

Endocannabinoids in the intact retina: 3 H-anandamide uptake, fatty acid amide hydrolase immunoreactivity and hydrolysis of anandamide.

There is much evidence for an endocannabinoid system in the retina. However, neither the distribution of endocannabinoid uptake, the regulation of endocannabinoid levels, nor the role of endocannabinoid metabolism have been investigated in the retina. Here we focused on one endocannabinoid, anandamide (AEA), and its major hydrolyzing enzyme, fatty acid amide hydrolase (FAAH), in the goldfish retina.

Reciprocal inhibition of voltage-gated potassium currents (I K(V)) by activation of cannabinoid CB1 and dopamine D1 receptors in ON bipolar cells of goldfish retina.

Cannabinoid CB1 receptor (via Gs) and dopamine D2 receptor (via Gi/o) antagonistically modulate goldfish cone membrane currents. As ON bipolar cells have CB1 and D1 receptors, but not D2 receptors, we focused on whether CB1 receptor agonist and dopamine interact to modulate voltage-dependent outward membrane K+ currents I K(V) of the ON mixed rod/cone (Mb) bipolar cells. Whole-cell currents were recorded from Mb bipolar cells in goldfish retinal slices.

Localization of vanilloid receptor 1 (TRPV1/VR1)-like immunoreactivity in goldfish and zebrafish retinas: restriction to photoreceptor synaptic ribbons.

The vanilloid receptor type 1 (TRPV1/VR1) is a non-specific calcium-permeable ionotropic cation channel expressed in the peripheral sensory system as well as in the central nervous system. An endogenous ligand for TRPV1 is arachidonoyl ethanolamide (anandamide), which also activates the metabotropic cannabinoid receptor 1 (CB1). Previous studies in this laboratory reported CB1 receptors and CB1-mediated effects on voltage-gated currents in goldfish cones and bipolar cells.

Vanilloid receptor like 1 (VRL1) immunoreactivity in mammalian retina: colocalization with somatostatin and purinergic P2X1 receptors.

The distribution of vanilloid receptor like1 immunoreactivity (VRL1-IR) in the retinas of rat, cat, and monkey was studied by single- and double-labeling immunocytochemistry. The patterns were similar for all three species in that VRL1-IR was most prominent in the inner plexiform layer, with scattered compact projections to the outer plexiform layer (OPL). VRL1-immunoreactive cell bodies were present throughout the rat retina, represented by amacrine cells in the inner nuclear layer and ganglion cell layer (GCL).

Postsynaptic localization of gamma-aminobutyric acid transporters and receptors in the outer plexiform layer of the goldfish retina: An ultrastructural study.

The gamma-aminobutyric acid (GABA)-ergic system in the outer plexiform layer (OPL) of the goldfish retina was studied via light and electron immunohistochemistry. The subcellular distributions of immunoreactivity (-IR) of plasma membrane GABA transporters GAT2 and GAT3, the alpha1 and alpha3 subunits of the ionotropic GABA(A) receptor, and the rho1 subunit of the ionotropic GABA(C) receptor were determined. The localization of the GAT2-IR and GAT3-IR to horizontal cell dendrites at the base of the cone synaptic complex was the main characteristic at the ultrastructural level.

Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones.

Dopamine is a light-adaptive signal that desensitizes the retina, while cannabinoids reportedly increase photosensitivity. The presynaptic membrane of goldfish retinal cones has dopamine D2 receptors and cannabinoid CB1 receptors. This work focused on whether dopamine D2 receptor agonist quinpirole and cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) interacted to modulate voltage-dependent membrane currents of cones.

Biphasic modulation of voltage-dependent currents of retinal cones by cannabinoid CB1 receptor agonist WIN 55212-2.

Endogenous cannabinoids modulate neurotransmitter action and release in the brain. The effects are exerted on membrane permeability to Ca2+ and K+ via protein kinase A (PKA). Cannabinoid CB1 receptors are present at the synaptic terminals of cones in goldfish retina.

Differential synaptic organization of GABAergic bipolar cells and non-GABAergic (glutamatergic) bipolar cells in the tiger salamander retina.

The synaptic organizations of gamma-aminobutyric acid-immunoreactive (GABA-IR, GABAergic) and non-GABA-IR (non-IR, glutamatergic) bipolar cells in salamander retina were compared by postembedding immunoelectron microscopy. A total of 238 presynaptic bipolar cell synapses were studied; 61 were GABA-IR and 177 were non-IR. Both groups were similar in that (1).

Neurochemical anatomy of the zebrafish retina as determined by immunocytochemistry.

The zebrafish retina is rapidly becoming a major preparation for the study of molecular genetic mechanisms underlying neural development and visual behavior. Studies utilizing retinal mutants would benefit by the availability of a data base on the distribution of neurotransmitter systems in the wild-type fish. To this end, the neurochemical anatomy of the zebrafish retina was surveyed by light microscopic immunocytochemistry.

Localization of the AMPA subunit GluR2 in the outer plexiform layer of goldfish retina.

L-glutamate, the photoreceptor neurotransmitter, depolarizes horizontal cells and OFF bipolar cells by ionotropic AMPA-glutamate receptors. The AMPA-receptor subunit (GluR4) is localized to dendrites of OFF bipolar cells in goldfish retina. Here, we used immunohistochemical techniques to identify AMPA-receptor subunits on horizontal cell dendrites.

Voltage-dependent sodium channels are expressed in nonspiking retinal bipolar neurons.

Retinal bipolar neurons transmit visual information by means of graded synaptic potentials that spread to the synaptic terminal without sodium-dependent action potentials. Although action potentials are not involved, voltage-dependent sodium channels may enhance subthreshold depolarizing potentials in the dendrites and soma of bipolar cells, as they do in other CNS neurons. We report here that voltage-dependent sodium currents are observed in a subset of bipolar neurons from goldfish retina.

Dopamine depletion with 6-OHDA enhances dopamine D1-receptor modulation of potassium currents in retinal bipolar cells.

Ascorbate modulates IK(V) of ON-type mixed rod/cone bipolar cells (Mb) in the goldfish retinal slice through a dopamine D1/G-protein/PKA-coupled mechanism. We investigated the effects of dopamine depletion with intraocular injections of 6-OHDA on IK(V) and its modulation by ascorbate over 1-7 weeks following 6-OHDA treatment. Dopamine depletion was verified by tyrosine hydroxylase immunocytochemistry.

Cannabinoid receptors on goldfish retinal bipolar cells: electron-microscope immunocytochemistry and whole-cell recordings.

Cannabinoid CB1 receptors are distributed throughout the CNS and interact with GABA, glutamate, and dopamine systems. Cannabinoids have effects on the visual system, some of which may have a retinal component, particularly the enhancement of photosensitivity. We used immunocytochemistry and whole-cell recording to study cannabinoids in the goldfish retina.

Immunocytochemical localization of the glutamate transporter GLT-1 in goldfish (Carassius auratus) retina.

Glutamate is the major excitatory neurotransmitter in the retina of vertebrates. Electrophysiological experiments in goldfish and salamander have shown that neuronal glutamate transporters play an important role in the clearance of glutamate from cone synaptic clefts. In this study, the localization of the glutamate transporter GLT-1 has been investigated immunocytochemically at the light and electron microscopical levels in the goldfish retina using a GLT-1-specific antibody.

Immunocytochemical localization of cannabinoid CB1 receptor and fatty acid amide hydrolase in rat retina.

Cannabinoids have major effects on central nervous system function. Recent studies indicate that cannabinoid effects on the visual system have a retinal component. Immunocytochemical methods were used to localize cannabinoid CB1 receptor immunoreactivity (CB1R-IR) and an endocannabinoid (anandamide and 2-arachidonylglycerol) degradative enzyme, fatty acid amide hydrolase (FAAH)-IR, in the rat retina.