The Journal of neuroscience : the official journal of the Society for Neuroscience
-
The epsilon4 allele of apolipoprotein E (apoE) is associated with increased risk for Alzheimer's disease (AD) and poor outcome after brain injury. In the CNS, apoE is expressed by glia, predominantly astrocytes. To define the potential biological functions of different human apoE isoforms produced within the brain, transgenic mice were generated in which human apoE3 and apoE4 expression is under control of the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter. ⋯ These effects are not dependent on direct astrocyte-neuron contact and appear to require the low-density lipoprotein receptor-related protein. These data suggest that astrocyte-secreted, apoE3-containing lipoproteins have different biological effects than apoE4-containing lipoproteins. In addition to providing information regarding the role of astrocyte-secreted apoE lipoproteins in the normal brain, these animals will also be useful in models of both AD and CNS injury.
-
To characterize further the establishment of the opioid system during prenatal mouse development, we have examined the spatial and temporal expression patterns of mu, kappa, and delta opioid receptor mRNAs and find that the expression patterns of these mRNAs are distinct at all ages. Within the embryo, kappa is the first opioid receptor expressed, with transcripts detected in the gut epithelium as early as embryonic day 9.5 (E9.5). By E10.5, mu receptor expression is first detected in the facial-vestibulocochlear preganglion complex, whereas delta receptor mRNA is first detected at E12.5 in several peripheral tissues, including the olfactory epithelium, heart, limb bud, and tooth. ⋯ Mu receptor is the first opioid receptor expressed in the spinal cord, at E11.5. These results extend previous ligand-binding data to significantly earlier ages and suggest that early developmental events in both neural and non-neural tissues may be modulated by opioid receptors. Several examples of possible autocrine and paracrine loops of opioid peptide and receptor expression have been identified, suggesting a role for these local circuits in developmental processes.
-
The medial temporal lobe (MTL) is essential for episodic memory encoding, as evidenced by memory deficits in patients with MTL damage. However, previous functional neuroimaging studies have either failed to show MTL activation during encoding or they did not differentiate between two MTL related processes: novelty assessment and episodic memory encoding. Furthermore, there is evidence that the MTL can be subdivided into subcomponents serving different memory processes, but the extent of this functional subdivision remains unknown. ⋯ Across participants, an ANOVA on the number of voxels with significant, positive correlations within individually defined volumes of interest confirmed a statistically significant difference in activation for anterior versus posterior regions of the hippocampus. However, no differences between left and right hippocampal activation were revealed. Thus, these findings demonstrate that successful encoding into episodic memory engages neural circuits in the posterior part of the hippocampus.
-
Unilateral limb-bud removal (LBR) before the outgrowth of sensory or motor neurons to the leg of chick embryos was used to examine the role of limb (target)-derived signals in the development and survival of lumbar motoneurons and sensory neurons in the dorsal root ganglia (DRG). After LBR, motor and sensory neurons underwent normal initial histological differentiation, and cell growth in both populations was unaffected. Before their death, target-deprived motoneurons also expressed a cell-specific marker, the homeodomain protein islet-1. ⋯ Taken together these data provide definitive evidence that the loss of spinal neurons after LBR cannot be attributed to altered proliferation, migration, or differentiation. Rather, in the absence of limb-derived trophic signals, the affected neurons fail to survive and undergo PCD. Although normal cell death and cell death after target deprivation share many features in common, the intracellular pathways of cell death in the two may be distinct.
-
Activation of the amygdala in rats produces cardiovascular changes that include increases in heart rate and arterial pressure as well as behavioral changes characteristic of emotional arousal. The objective of the present study was to examine the interaction of GABA and excitatory amino acid (EAA) receptors in the basolateral amygdala (BLA) in regulating cardiovascular function. Microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) or the E A A receptor agonists NMDA or AMPA into the same region of the BLA of conscious rats produced dose-related increases in heart rate and arterial pressure. ⋯ The cardiovascular effects of BMI were also attenuated by injection of either the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or the AMPA receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX). When these two EAA receptor antagonists were combined, their ability to suppress BMI-induced tachycardic and pressor responses was additive. These findings indicate that the cardiovascular effects caused by blockade of GABAergic inhibition in the BLA of the rat are dependent on activation of local NMDA and AMPA receptors.