Reductions in N‐acetylaspartylglutamate and the 67 kDa form of glutamic acid decarboxylase immunoreactivities in the visual system of albino and pigmented rats after optic nerve transections

Abstract

This study compares the immunohistochemical distributions of N-acetylaspartylglutamate (NAAG) and the large isoform of the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD(67)) in the visual system of albino and pigmented rats. Most retinal ganglion cells and their axons were strongly immunoreactive for NAAG, whereas GAD(67) immunoreactivity was very sparse in these cells and projections. In retinorecipient zones, NAAG and GAD(67) immunoreactivities occurred in distinct populations of neurons and in dense networks of strongly immunoreactive fibers and synapses. Dual-labeling immunohistochemistry indicated that principal neurons were stained for NAAG, whereas local interneurons were stained for GAD(67). In contrast to the distribution observed in retinorecipient zones, most or all neurons were doubly stained for NAAG and GAD(67) in the thalamic reticular nucleus. Ten days after unilateral optic nerve transection, NAAG-immunoreactive fibers and synapses were substantially reduced in all contralateral retinal terminal zones. The posttransection pattern of NAAG-immunoreactive synaptic loss demarcated the contralateral and ipsilateral divisions of the retinal projections. In addition, an apparent transynaptic reduction in GAD(67) immunoreactivity was observed in some deafferented areas, such as the lateral geniculate. These findings suggest a complicated picture in which NAAG and GABA are segregated in distinct neuronal populations in primary visual targets, yet they are colocalized in neurons of the thalamic reticular nucleus. This is consistent with NAAG acting as a neurotransmitter release modulator that is coreleased with a variety of classical transmitters in specific neural pathways.

NAAG Peptidase Inhibition in the Periaqueductal Gray and Rostral Ventromedial Medulla Reduces Flinching in the Formalin Model of Inflammation

“…Consistent with the potential of this transmitter to regulate neurotransmission via activation of presynaptic receptors in these brain regions, putative NAAGergic synapses were observed on the cell bodies and dendrites of PAG neurons, as well as in the neuropil (Figure 1c). While these data alone are insufficient to confirm the synaptic localization of this immunoreactivity, studies with this antibody at the ultrastructural level previously localized NAAG immunoreactivity to synaptic vesicles [30] and optic nerve transection studies demonstrated that NAAG immunoreactivity is associated with NAAG-containing synaptic terminals in various regions of the CNS [31,32]. Additionally, depolarization-induced calcium-dependent NAAG release has been demonstrated repeatedly [10,33].…”

Modulation of GABAergic inhibition in the rat superior colliculus by a presynaptic group II metabotropic glutamate receptor

“…In contrast, the endogenous dipeptide N -acetyl-aspartyl-glutamate (NAAG) selectively activates mGluR3 with an EC 50 of less than 100 μm whilst producing no significant activation of mGluR2 receptors at 1 mm (Wroblewska et al 1997). Furthermore, NAAG is expressed strongly in retinal ganglion cells (Moffett, 2003), is released in the SC C 2006 The Authors. Journal compilation C 2006 The Physiological Society following optic tract stimulation (Tsai et al 1990) and has been proposed to function as a neurotransmitter (Neale et al 2000;Gafurov et al 2001).…”

Antipsychotic drugs increase N‐acetylaspartate and N‐acetylaspartylglutamate in SH‐SY5Y human neuroblastoma cells

“…It is thought that the alterations in GABAergic neurotransmission lead to dysregulation of glutamatergic activity, which in turn is responsible in part for the pathophysiology of schizophrenia. NAAG is expressed extensively in interneurons of neocortex in rat (Moffett and Namboodiri 1995), and monkey (Moffett and Namboodiri 2006), and is colocalized with the GABA synthesizing enzyme glutamic acid decarboxylase (Moffett 2003). Because NAAG has been shown to reduce glutamate release (Xi et al.…”