Deep Layers Of Frontal Cortex Research Articles

Expression of apoptosis-inducing factor (AIF) in the aged rat brain

The mitochondrial flavoprotein apoptosis-inducing factor (AIF) promotes cell death upon nuclear translocation or by impinging on mitochondrial respiratory complex-I activity. Because decreased complex-I activity is associated with brain aging, we investigated the expression and distribution of AIF in frontal cortex, hippocampus and striatum of aged Long-Evans rat brains. We found that AIF was: (i) more abundantly expressed in striatum than in the other two brain regions, (ii) enriched in deep layers of frontal cortex and in the pyramidal cell layer of hippocampus, and (iii) overall mainly localized to mitochondria, but significantly more translocated to the nucleus in the deep layers of frontal cortex. Altogether, our data point to a difference in region 1 AIF expression patterns, and provide evidence for the involvement of AIF in the cell death of a subpopulation of cortical neurons in aged animals.

Antidepressants Influence Somatostatin Levels and Receptor Pharmacology in Brain

This study investigated how the administration (acute and chronic) of the antidepressants citalopram and desmethylimipramine (DMI) influences somatostatin (somatotropin release inhibitory factor, SRIF) levels and SRIF receptor density (sst(1-5)) in rat brain. Animals received either of the following treatments: (1) saline for 21 days (control group), (2) saline for 20 days and citalopram or DMI for 1 day (citalopram or DMI acute groups), (3) citalopram or DMI for 21 days (citalopram or DMI chronic groups). Somatostatin levels were determined by radioimmunoassay. [(125)I]LTT SRIF-28 binding in the absence (labeling of sst(1-5)) or presence of 3 nM MK678 (labeling of sst(1/4)) and [(125)I]Tyr(3) octreotide (labeling of sst(2/5)) binding with subsequent autoradiography was performed in brains of rats treated with both antidepressants. Somatostatin levels were increased after citalopram, but not DMI administration, in the caudate-putamen, hippocampus, nucleus accumbens, and prefrontal cortex. Autoradiography studies illustrated a significant decrease in receptor density in the superficial and deep layers of frontal cortex (sst(2)), as well as a significant increase in the CA1 (sst(1/4)) hippocampal field in brains of chronically citalopram-treated animals. DMI administration increased sst(1/4) receptors levels in the CA1 hippocampal region. These results suggest that citalopram and to a lesser extent DMI influence the function of the somatostatin system in brain regions involved in the emotional, motivational, and cognitive aspects of behavior.

Regional brain glucose utilization following intrastriatal injections of kainic acid

Regional brain glucose utilization following intrastriatal injections of kainic acid (KA) was studied by [ 14C]deoxyglucose autoradiography. In halothane anesthetized rats intrastriatal injections of 0.5–1.9 nmol KA produced histological lesions characterized by neuronal necrosis and glial reaction which varied in volume from approximately 3 to 25 cu. mm. These lesions were restricted to the striatal injection site. Intrastriatal injections of 3.8 nmol led to large lesions in striatum but also in ipsilateral hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. Injection doses of 0.5–3.8 nmol KA produced a large increase in striatal glucose utilization within 1 h; 7 days after injections however, glucose utilization was reduced below control levels in a dose-dependent manner. In addition to striatum there were large transient increases in glucose utilization in deep layers of frontal cortex, substantia nigra pars reticulata, ventral tier nuclei of thalamus, and lateral septum. Each of these structures bear close physical or synaptic proximity to the striatal injection site. Also, structures far distant from the striatal injection site exhibited large, transient, dose-dependent increases in glucose utilization; these regions included hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. There was a close correlation between the development of areas of neuronal necrosis and a reduction in glucose utilization. These results suggest that intrastriatal injections of KA may cause metabolic and perhaps electrical activation not only of structures near of synaptically connected to the injection site, but also of far distant, but particularly ‘sensitive’ brain structures probably by diffusion of small amounts of drug. The occurence of neuronal death in limbic structures after injections of relatively high doses of KA into striatum may result from prolonged firing in those circuits which continues without the prolonged presence of KA. The use of KA as a lesioning tool requires careful histological controls. The lack of such controls renders some behavioral and pharmacological studies of KA-lesioned animals difficult to interpret.