Distribution of β‐nerve growth factor receptors in the human basal forebrain

Abstract

The distribution of neurons expressing the receptor for beta-nerve growth factor has been examined immunohistochemically in serial coronal sections of basal forebrain from aged normal human subjects. Neurons expressing the receptor were observed in the nucleus of the diagonal band of Broca and in the anterior, the intermediate, and the posterior portions of the nucleus basalis of Meynert. Neurons could also be seen in the medial septal nucleus and embedded in myelinated fibre tracts such as those of the external capsule, cingulum, medullary laminae of the globus pallidus, ansa penduncularis, ansa lenticularis, and anterior commissure. In situ hybridization with a 35S cDNA probe to the human beta-nerve growth factor receptor confirms a neuronal location as the site of synthesis of beta-nerve growth factor receptors in the nucleus basalis of Meynert in a fifth brain. A high percentage of Nissl-stained hyperchromic magnocellular neurons expressed the receptor for beta-nerve growth factor, suggesting that most neurons in the human cholinergic magnocellular basal forebrain system express these receptors. Recent data suggest that beta-nerve growth factor functions as a neurotrophic factor in basal forebrain cholinergic neurons. In Alzheimer's disease there is known to be a reduction in cholinergic function and an apparent loss of neurons in the cholinergic nucleus basalis of Meynert. For this reason we have examined the distribution of receptors for beta-nerve growth factor in the normal human basal forebrain in order to form a basis for comparison to those with Alzheimer's disease.

Populations of subplate and interstitial neurons in fetal and adult human telencephalon

“…That concept of a neuronal shell enclosing the globus pallidus was extensively confirmed in subsequent studies of the magnocellular cholinergic basal forebrain system in both human and monkey, by means of various markers of these neurons such as AChE, choline-acetyltransferase, nerve growth factor and nerve growth factor receptors (trk1, p75). Displaced cholinergic neurons (usually interpreted as belonging to the Ch4 group or basal nucleus of Meynert) were documented within the internal and external capsule, anterior commissure and medullary laminae separating two segments of the globus pallidus as well as the globus pallidus from the putamen (Mesulam et al 1983;Mesulam & Mufson, 1984;Satoh & Fibiger, 1985;Kordower et al 1988Kordower et al , 1989Kordower et al , 1994Mesulam & Geula, 1988;Allen et al 1989;Mufson et al 1989). Although there is no clear evidence that these cholinergic neurons also synthesize nitric oxide, NADPH-d-positive fibres were noted in the human external capsule (Ellison et al 1987) and NOS-immunoreactive neurons (Satoh et al 1995), and neuropeptide Y-immunoreactive neurons were found in the monkey external capsule and medullary laminae surrounding human globus pallidus (Lehé ricy et al 1993).…”

Quantitative Morphometric Analysis of Basal Forebrain Neurons Expressing β-Nerve Growth Factor Receptors in Normal and Alzheimer's Disease Brains

“…The majority of magnocellular neurons in these nuclei are P-NGF receptor positive [24], and there appears to be a high degree of colocalization between ChAT-positive and (3-NGF-receptor-immunoreactive neurons [19]. In situ hybridization using a radiolabelled cDNA probe to the human p-NGF receptor has confirmed magnocel lular neurons as the site of synthesis of p-NGF receptors [24,25].…”

“…This monoclonal antibody binds to the human low-affinity P-NGF recep tor and blocks the binding of [l2SI]-p-NGF to SK-MEL-13 mela noma cells {36]. Immunohistochemical staining was carried out as described previously [24]. Briefly, coronal sections (30 pm thick) were cut on a freezing microtome and collected in triplicate, free floating, every 300 pm.…”

“…Cholinergic neurons of the NDBB and the NBCh4 have been visualized in human brain using an antibody to ChAT [18,[20][21][22], and, more recently, by using a monoclonal antibody to the |3-NGF receptor [ 19,23,24]. The majority of magnocellular neurons in these nuclei are P-NGF receptor positive [24], and there appears to be a high degree of colocalization between ChAT-positive and (3-NGF-receptor-immunoreactive neurons [19].…”

The role of nerve growth factor in Alzheimer's disease

“…NGF-receptors are expressed on the cholinergic neurons of the basal forebrain and can be demonstrated on their dendrites in the target areas (Allen et al 1989). This suggests that NGF is produced by these target areas so as to be retrogradely transported to the cholinergic cell bodies in the basal forebrain area.…”