Excitatory neurotransmitters in brain regions in interictal migraine patients.

OBJECTIVE: To examine biochemical differences in the anterior cingulate cortex (ACC) and insula during the interictal phase of migraine patients. We hypothesized that there may be differences in levels of excitatory amino acid neurotransmitters and/or their derivatives in migraine group based on their increased sensitivity to pain. METHODS: 2D J-resolved proton magnetic resonance spectroscopy (1H-MRS) data were acquired at 4.0 Tesla (T) from the ACC and insula in 10 migraine patients (7 women, 3 men, age 43 +/- 11 years) and 8 age gender matched controls (7 women, 3 men, age 41 +/- 9 years). RESULTS: Standard statistical analyses including analysis of variance (ANOVA) showed no significant metabolite differences between the two subject cohorts in the ACC nor the insula. However, linear discriminant analysis (LDA) introduced a clear separation between subject cohorts based on N-acetyl aspartylglutamate (NAAG) and glutamine (Gln) in the ACC and insula. CONCLUSION: These results are consistent with glutamatergic abnormalities in the ACC and insula in migraine patients during their interictal period compared to healthy controls. An alteration in excitatory amino acid neurotransmitters and their derivatives may be a contributing factor for migraineurs for a decrease in sensitivity for migraine or a consequence of the chronic migraine state. Such findings, if extrapolated to other regions of the brain would offer new opportunities to modulate central system as interictal or preemptive medications in these patients.

Localization of excitatory amino acid and neuropeptide markers in neurons of the subicular complex projecting to the retrosplenial granular cortex of the rat / Caracterización inmunocitoquímica de marcadores excitadores aminoacidérgicos y neuropeptidérgicos en neuronas del complejo subicular que proyectan a la corteza granular retroesplenial de la rata

Retrograde labelling was combined with immunohistochemistry to localize neurons containing glutamate and different neuropeptides such as neurotensin, leu-enkephalin, and substance P-like immunoreactivity in the projection pathways from the presubiculum and subiculum to the retrosplenial granular cortex of the rat. Injections of horseradish peroxidase conjugated to subunit B of cholera toxin (CT-HRP) into the retrosplenial granular cortex labelled large numbers of neurons in the presubiculum. A significant number of retrogradely-labelled neurons was seen in the dorsal subiculum, whereas small numbers of CT-HRP-labelled neurons were also found in the ventral subiculum. In the presubiculum, 90-95% of the CT-HRP-labelled neurons (30-32 per section) were also immunoreactive for glutamate, and small numbers of retrogradely-labelled neurons also displayed neurotensin-, leu-enkephalin- or substance P-immunoreactivity. In the subiculum, approximately 90-95% of the CT-HRP-labelled neurons (19-20 per section) were also immunoreactive for glutamate, and a significant number of retrogradely-labelled neurons (70-75%, 14-15 per section) also displayed neurotensin immunoreactivity. In addition, small numbers of CT-HRP-labelled neurons in the subiculum were immunoreactive for leu-enkephalin or substance P. These results suggest that the complexity of the neurotransmitter(s)/neuromodulator(s) of the subicular projections to the retrosplenial granular cortex of the rat should be taken into account when considering the mechanisms of the retrosplenial cortical neurons thought to play a role in memory (AU)

En ratas (Wistar, 250-300 g), se realizaron microinyecciones (0.2?l-0.6?l) de una solución acuosa al 2 por ciento de peroxidasa de rábano conjugada con la toxina del cólera (CT-HRP) en diferentes regiones de la corteza retroesplenial (parte caudal de la corteza cingular). Tras periodos de supervivencia entre 24 y 48 horas, los animales se perfundieron con una solución de paraformaldehido al 2 por ciento y glutaraldehido al 0.1 por ciento en solución tampón de fosfato (pH 7.2). Los cerebros se seccionaron en vibratomo y series adyacentes de 50 µm de grosor se procesaron para poner de manifiesto la presencia de CT-HRP mediante una reacción histoquímica utilizando tetrametilbenzidina (TMB) como crómogeno y la distribución de neuronas inmunorreactivas ante glutamato y ante diversos neuropéptidos, como neurotensina, encefalina y substancia P, utilizando DAB como cromogeno y técnicas de inmunocitoquímica con antisueros anti-glutamato, anti-neurotensina, anti-encefalina y anti-substancia P. El análisis del material muestra la presencia de diversas poblaciones neuronales marcadas retrógradamente por el complejo CT-HRP en la corteza hipocampal, especialmente en el presubiculum y en la región dorsal del subiculum, y por lo tanto son neuronas de proyección a la zona de inyección en la corteza retroesplenial. En el presubiculum el 90-95 por ciento de las neuronas marcadas retrógradamente eran inmunorreactivas ante glutamato y una pequeña proporción de neuronas de proyección al lugar diana expresaban inmunorreactividad ante los diferentes sistemas neuropeptidérgicos analizados, neurotensina, encefalina o substancia P. En el subiculum, aproximadamente el 90-95 por ciento de las neuronas marcadas retrógradamente expresaban inmunorreactividad ante glutamato y una población neuronal significativa, entre el 70-75 por ciento, expresaba inmunorreactividad ante neurotensina. Además, en el subiculum se apreció una pequeña población de neuronas marcadas retrógradamente por el complejo CT-HRP inmunopositivas ante encefalina o substancia P. En conclusión, el estudio indica que la proyección de la corteza hipocampal (subiculum y presubiculum) a la corteza cingular está mediada por diversos sistemas de neurotransmisión, esencialmente aminoácidos excitadores y neuropeptidos, y sugiere que el complejo sistema de neurotransmisión hipocampo-cortical (corteza cingular) puede tener un papel importante en los mecanismos cognitivos en los que está implicado este sistema, tales como memoria y aprendizaje (AU)