Coexistence of glutamate decarboxylase and somatostatin immunoreactivity in cultured hippocampal neurons of the rat

The immunoperoxidase-antiperoxidase method (PAP) was combined with immunofluorescence for simultaneous localization of glutamate decarboxylase (GAD)-and somatostatin-like immunoreactivity in rat hippocampal neurons growing in dissociated cell culture. A subpopulation of GAD-immunoreactive neurons additionally exhibited somatostatin-like immunostaining. GAD-negative somatostatin-positive cells could not be observed. It is discussed whether the cultured somatostatin-containing GAD neurons correspond to a certain subclass of basket cells as they occur in situ.     

大鼠新生期皮下注射谷氨酸单钠对成年后下丘脑ACTH神经元和正中隆起CRF神经纤维免疫反应性的影响

本文采用过氧化酶—抗过氧化酶(PAP)的免疫组织化学和荧光免疫组织化学的方法,研究了新生期大鼠皮下注射谷氨酸单纳(MSG)对成年后下丘脑弓状核促肾上腺皮质激素(ACTH)神经元和正中隆起内促肾上腺皮质激素释放因子(CRF)神经纤维免疫反应的影响。新生期MSG处理后,弓状核中ACTH神经元的数目明显减少,正中隆起CRF样免疫反应末稍也大大减少,减少程度随MSG剂量增大而增加。提示MSG通过损伤前阿黑皮素(POMC)衍生的神经多肽,从而影响下丘脑—垂体—肾上腺皮质轴的功能。     

Effect of N-phthalamoyl-L-glutamic acid,a selective NMDA receptor agonist,on binding of3H-L-glutamate with hippocampal synaptic membranes

Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg. (Presented by Academician of the Russian Academy of Medical Sciences A. N. Klimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 6, pp. 563–565, June, 1992.     

Are glutamate receptors specifically implicated in some forms of memory processes?

Convergent data indicate that certain substances that interact with N-methyl-d-aspartate (NMDA) receptors or metabotropic glutamate receptors (mGluRs) do not affect acquisition processes per se, or retrieval, but interfere specifically with the formation of memory traces. This action differs widely in its amplitude and time-course according to the learning task used. We showed that systemic injection of the competitive NMDA receptor antagonists, γ-l-glutamyl-l-aspartate (γ-LGLA) and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), or intracerebroventricular infusion of d-2-amino-5-phosphonovalerate (D-AP5), immediately following acquisition of a Y-maze avoidance learning task in mice, deeply impaired retention of the temporal component of the task (leaving the start alley within the first 5 s of a trial), which significantly improved in controls during the hours following acquisition. In contrast the same substances had no or only slight effects on retention of the discrimination component (choice of the correct alley), which did not improve over time in control animals. This retention deficit did not appear to be due to an action on acquisition, retrieval and/or forgetting processes, or to state-dependent effects. Moreover, γ-LGLA, CPP or AP5, when administered immediately after partial acquisition of a food-reinforced bar-press task, suppressed the spontaneous improvement in post-training performance observed in control mice 24 h after the training session. (R,S)-α-methyl-4-carboxyphenylglycine (MCPG), an antagonist of mGluRs, also suppressed the post-training performance increment and its effects were antagonized by the co-administration of trans-ACPD, an agonist of mGluRs. Post-training improvement of performance over time is thought to reflect an active and dynamic process, leading to the organization of memory traces. According to this hypothesis, our results suggest that synaptic plasticity mediated by NMDA receptors and/or mGluRs activation is involved in mechanisms underlying long-term consolidation of memory traces.     

Modification of Redox Sites of N-Methyl-D-Aspartate Receptors Affects Anoxia-Induced Changes in the Bioelectrical Activity of Rat Brain Olfactory Cortex Slices

Living slices of Wistar-Kyoto rat brain olfactory cortex were used to study the effects of the thiol-oxidizing agent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), which inhibits NMDA receptor activity, on changes in the generation of evoked focal potentials (NMDA and non-NMDA EPSP) in response to long-term and short-term anoxia, which induces functional damage and facilitates increases in the resistance of neurons to severe hypoxia respectively. These studies showed that DTNB (200 'M) efficiently prevented the suppression of focal EPSP generation due to long-term anoxia in most slices. In addition, DTNB partially reversed the protective effect of preconditioning with short-term anoxia on the impairment of focal EPSP generation induced by long-term anoxia. This affected the NMDA component of the EPSP to a greater extent than the non-NMDA component. The possible role of changes in the state of modulatory redox sites of NMDA receptors in the mechanisms of functional damage and increases in neuron resistance due to hypoxia is discussed.     

Comparison of Changes in Glutamate Levels in the Nucleus Accumbens of the Rat Brain during Food Consumption in Conditions of Blockade of Dopamine D1 and D2 Receptors

The effects of blockade of D₁ and D₂ dopamine receptors in the nucleus accumbens on changes in glutamate levels in the intercellular space of this structure during food consumption were studied in Sprague–Dawley rats by intracerebral microdialysis combined with HPLC. These experiments showed that food consumption was accompanied by decreases in glutamate levels in the intercellular spaces of the nucleus accumbens. Blockade of D₁ dopamine receptors with SCH-23390 (0.01 mM) produced no changes in the dynamics of glutamate release during food consumption. Food consumption in conditions of blockade of D₂ dopamine receptors with raclopride (0.01 mM) induced increases in glutamate levels. These data suggest that glutamate levels during food consumption are controlled by the dopaminergic system of the nucleus accumbens, mediated by D₂ but not D₁ dopamine receptors.     

The involvement of glutamatergic transmission in the mechanism of movement disorders induced by reversive rotation of white mice

The ability of the selective non-competitive NMDA receptor blocker MK-801 and a series of new glutamate antagonists—the adamantane derivatives IEM-1754 and IEM-1857 and phencyclidine (IEM-1925)—to prevent movement disorders induced by reversive rotation in mice was studied. I.p. MK-801 at a dose of 0.15 ml and IEM-1754 at a dose of 5.0 mg/kg prevented the development of akinesia in response to reversive rotation, as effectively as scopolamine, a known agent which provides effective prophylaxis for movement diseases. IEM-1857, the quaternary analog of IEM-1754, was not effective. IEM-1925 significantly increased the responses of mice to reversive rotation, possibly because of its high activity in relation to other subtypes of glutamate receptors. These data provide evidence for the involvement of glutamatergic transmission in the mechanism of movement disorders of vestibular origin. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 4, pp. 497–501, May, 1999.     

Chronic morphine treatment increases the expression of the neural cell adhesion molecule in the dorsal horn of the mouse spinal cord

It is well known that prolonged exposure to morphine results in tolerance to morphine-induced antinociception. In the present study, we found that mice that were tolerant to morphine-induced antinociception exhibited an increase in immunoreactivity for the neural cell adhesion molecule in the dorsal horn of the spinal cord, which was highly overlapped with immunoreactivity for the increased metabotropic glutamate receptor 5 induced by morphine. These findings support the idea that repeated stimulation of μ-opioid receptors increases the expression of neural cell adhesion molecule and metabotropic glutamate receptor 5. This phenomenon leads to the enhanced excitatory synaptic transmission in the dorsal horn of the spinal cord, and in turn suppresses the morphine-induced antinociception.     

Caudal end of the rat spinal dorsal horn

We have previously demonstrated that the transformation of the caudal spinal cord through the conus medullaris to the filum terminale takes place in three steps. In the conus medullaris the twin layers of CGRP-immunoreactive and IB4-labeled primary afferent fibers as well as the translucent portion of the superficial dorsal horn equivalent to the substantia gelatinosa discontinue before the complete removal of the dorsal horn. Parallel with these changes VGLUT1-immunoreactive myelinated primary afferent fibers arborize not only in the deep layers but also in the entire extension of the remaining dorsal horn, while scattered CGRP fibers still remains at the margin of and deep in the dorsal horn. PKCgamma-immunoreactive dorsal horn neurons discontinue parallel with the disappearance of the IB4-labeled nerve fibers. These observations suggest that in the dorsal horn certain neurons are linked to the substantia gelatinosa, while others are substantia gelatinosa-independent neurons.