Selective lesion of the cholinergic basal forebrain causes a loss of cortical neuropeptide Y and somatostatin neurons. 1998

Z J Zhang, and D A Lappi, and C C Wrenn, and T A Milner, and R G Wiley
Laboratory of Experimental Neurology, Neurology Service (127), DVAMC, 1310 24th Avenue, South, Nashville, TN 37212-2637, USA.

Degeneration of the cholinergic basal forebrain (CBF) and changes in cortical neuropeptide levels have been reported in Alzheimer's disease. In the present study, we sought to determine if a selective cholinergic lesion of nucleus basalis magnocellularis (Nbm) could affect the number and distribution of neuropeptide Y (NPY) and somatostatin (SS) immunoreactive neurons in the frontoparietal and occipital cortices of rats. Brain sections were evaluated at survival times of 1, 2, 4, 8, 12, 24, 48, 78 and 100 weeks after intraventricular injection of 192-saporin, an immunotoxin directed at the low affinity neurotrophin receptor (p75NGFr), that selectively destroys the CBF. Following the immunotoxin lesion of the Nbm, the number of NPY-labeled neurons decreased 33% in the frontoparietal cortex and 60% in the occipital cortex compared to age-matched normal controls at most survival time points. A significant loss of SS-labeled neurons in both cortical regions was seen 12 weeks after 192-saporin injection with no further change up to 100-week survival time. The effect of age on neuropeptidergic populations was evaluated in normal control rats. The number of NPY and SS immunoreactive neurons in aged rats (21-26 months) decreased by 42% in the frontoparietal cortex and 27% in the occipital cortex when compared with young (3-6 months) and middle-age (9-14 months) rats. When both non-lesioned and lesioned animals with different ages were pooled for linear regression, a significant correlation was found between the number of cortical NPY- and SS-labeled neurons and cortical acetylcholinesterase (AChE) histochemical staining intensity. These findings indicate that: (1) cholinergic denervation of the Nbm is associated with an irreversible loss of neocortical NPY and SS immunoreactive neurons analogous to that observed in Alzheimer's disease and aging; (2) the degree of the loss of cortical NPY and SS immunoreactive neurons seems to be related to the extent of the reduction of cortical AChE intensity in both toxin-injected and normal aged rats. These findings may reflect a trophic dependence of NPY and SS neurons on cortical cholinergic input.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D009478 Neuropeptide Y A 36-amino acid peptide present in many organs and in many sympathetic noradrenergic neurons. It has vasoconstrictor and natriuretic activity and regulates local blood flow, glandular secretion, and smooth muscle activity. The peptide also stimulates feeding and drinking behavior and influences secretion of pituitary hormones. Neuropeptide Y-Like Immunoreactive Peptide,Neuropeptide Tyrosine,Neuropeptide Y Like Immunoreactive Peptide,Tyrosine, Neuropeptide
D009778 Occipital Lobe Posterior portion of the CEREBRAL HEMISPHERES responsible for processing visual sensory information. It is located posterior to the parieto-occipital sulcus and extends to the preoccipital notch. Annectant Gyrus,Calcarine Fissure,Calcarine Sulcus,Cuneate Lobule,Cuneus,Cuneus Cortex,Cuneus Gyrus,Gyrus Lingualis,Lingual Gyrus,Lunate Sulcus,Medial Occipitotemporal Gyrus,Occipital Cortex,Occipital Gyrus,Occipital Region,Occipital Sulcus,Sulcus Calcarinus,Calcarine Fissures,Calcarinus, Sulcus,Cortex, Cuneus,Cortex, Occipital,Cortices, Cuneus,Cortices, Occipital,Cuneate Lobules,Cuneus Cortices,Fissure, Calcarine,Fissures, Calcarine,Gyrus Linguali,Gyrus, Annectant,Gyrus, Cuneus,Gyrus, Lingual,Gyrus, Medial Occipitotemporal,Gyrus, Occipital,Linguali, Gyrus,Lingualis, Gyrus,Lobe, Occipital,Lobes, Occipital,Lobule, Cuneate,Lobules, Cuneate,Occipital Cortices,Occipital Lobes,Occipital Regions,Occipitotemporal Gyrus, Medial,Region, Occipital,Regions, Occipital,Sulcus, Calcarine,Sulcus, Lunate,Sulcus, Occipital
D010296 Parietal Lobe Upper central part of the cerebral hemisphere. It is located posterior to central sulcus, anterior to the OCCIPITAL LOBE, and superior to the TEMPORAL LOBES. Brodmann Area 39,Brodmann Area 40,Brodmann Area 5,Brodmann Area 7,Brodmann's Area 39,Brodmann's Area 40,Brodmann's Area 5,Brodmann's Area 7,Inferior Parietal Cortex,Secondary Sensorimotor Cortex,Superior Parietal Lobule,Angular Gyrus,Gyrus Angularis,Gyrus Supramarginalis,Intraparietal Sulcus,Marginal Sulcus,Parietal Cortex,Parietal Lobule,Parietal Region,Posterior Paracentral Lobule,Posterior Parietal Cortex,Praecuneus,Precuneus,Precuneus Cortex,Prelunate Gyrus,Supramarginal Gyrus,Area 39, Brodmann,Area 39, Brodmann's,Area 40, Brodmann,Area 40, Brodmann's,Area 5, Brodmann,Area 5, Brodmann's,Area 7, Brodmann,Area 7, Brodmann's,Brodmanns Area 39,Brodmanns Area 40,Brodmanns Area 5,Brodmanns Area 7,Cortex, Inferior Parietal,Cortex, Parietal,Cortex, Posterior Parietal,Cortex, Precuneus,Cortex, Secondary Sensorimotor,Cortices, Inferior Parietal,Gyrus, Angular,Gyrus, Prelunate,Gyrus, Supramarginal,Inferior Parietal Cortices,Lobe, Parietal,Lobule, Parietal,Lobule, Posterior Paracentral,Lobule, Superior Parietal,Paracentral Lobule, Posterior,Paracentral Lobules, Posterior,Parietal Cortex, Inferior,Parietal Cortex, Posterior,Parietal Cortices,Parietal Cortices, Inferior,Parietal Cortices, Posterior,Parietal Lobes,Parietal Lobule, Superior,Parietal Lobules,Parietal Lobules, Superior,Parietal Regions,Posterior Paracentral Lobules,Posterior Parietal Cortices,Precuneus Cortices,Region, Parietal,Secondary Sensorimotor Cortices,Sensorimotor Cortex, Secondary,Superior Parietal Lobules
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D002799 Cholinergic Fibers Nerve fibers liberating acetylcholine at the synapse after an impulse. Cholinergic Fiber,Fiber, Cholinergic,Fibers, Cholinergic
D005625 Frontal Lobe The part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus. Brodmann Area 8,Brodmann's Area 8,Frontal Cortex,Frontal Eye Fields,Lobus Frontalis,Supplementary Eye Field,Area 8, Brodmann,Area 8, Brodmann's,Brodmanns Area 8,Cortex, Frontal,Eye Field, Frontal,Eye Field, Supplementary,Eye Fields, Frontal,Frontal Cortices,Frontal Eye Field,Frontal Lobes,Lobe, Frontal,Supplementary Eye Fields
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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