Perineuronal nets in the rhesus monkey and human basal forebrain including basal ganglia

doi:10.1016/S0306-4522(01)00419-5

Neuroscience

Volume 108, Issue 2, 10 December 2001, Pages 285-298

https://doi.org/10.1016/S0306-4522(01)00419-5 Get rights and content

Abstract

Perineuronal nets of extracellular matrix have been shown to characterize the microenvironment of individual neurons and the chemoarchitecture of brain regions such as basal forebrain nuclei. Previous work has also demonstrated that neurons in the human cerebral cortex ensheathed by perineuronal nets rarely undergo cytoskeletal changes in Alzheimer’s disease, suggesting a neuroprotective effect of extracellular matrix components. It is not known, however, whether or not perineuronal nets are absent in the microenvironment of the cholinergic basal forebrain neurons that are involved early in the cascade of neurodegeneration in humans. Therefore, the present study was undertaken to examine the distribution patterns of perineuronal nets in the basal forebrain of the higher primates, rhesus monkey and human.

Cytochemical staining was performed with the lectin Wisteria floribunda agglutinin and a polyclonal antibody to core proteins of chondroitin sulfate proteoglycans in the perfusion-fixed tissue of rhesus monkeys. In human brains, perineuronal nets were only stained with the immunoreaction for chondroitin sulfate proteoglycans. The results showed similar characteristics in distribution patterns of perineuronal nets in the medial septum, the diagonal band of Broca, the basal nucleus of Meynert (Ch1–Ch4), the lateral septum, the caudate–putamen, and the globus pallidus in both species. Double-labelling revealed that the vast majority of cholinergic neurons, labelled either with antibodies to choline acetyltransferase or the low-affinity neurotrophin receptor p75^NTR, were not ensheathed by perineuronal nets. A small subpopulation of net-associated neurons in close proximity to or intermingled with cholinergic neurons of the Ch1–Ch4 cell groups was found to be immunoreactive for parvalbumin. In the caudate–putamen, a large number of the parvalbumin-positive neurons were surrounded by perineuronal nets, whereas in the external and internal segments of the globus pallidus the coincidence of both markers was nearly complete.

The study demonstrates that perineuronal nets of extracellular matrix are associated with different types of non-cholinergic neurons in the primate basal forebrain. The absence of nets around cholinergic basal forebrain neurons may be related to their slow modulatory activity but may also contribute to their susceptibility to degeneration in Alzheimer’s disease.

Section snippets

Tissue preparation

Tissue samples containing the basal forebrain from four adult rhesus monkeys (Macaca mulatta; one female, 6 years old, one male, 3–4 years old, two males, 28 years old) were kindly provided by Dr. J.A. Büttner-Ennever (Ludwig Maximilians University, Munich, Germany) as a remainder of her approved tract tracing experiments focused on the caudal brainstem and cerebellar components of the oculomotor system. This tissue had been perfused with 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4

Staining of extracellular matrix components in the rhesus monkey and human brain tissue

Previous work in the rat and several other mammals has demonstrated that WFA staining and immunoreaction for CSPG core proteins reveal largely congruent distribution patterns of the PNs (Härtig et al., 1994, Köppe et al., 1997, Brückner et al., 2000). In the present study, WFA showed excellent staining in the four perfusion-fixed monkey brains but the staining was absent or extremely weak in autoptic human basal forebrain. Therefore, to make the results reliably comparable, we used CSPG

Discussion

The present study shows for the first time that extracellular matrix components that reacted with two general markers of PNs, the lectin WFA and CSPG antibodies, are distributed in region-specific patterns in the primate basal forebrain, similar to those previously described in non-primate mammals (Brauer et al., 1993, Brauer et al., 1995, Brauer et al., 1999, Brückner et al., 1994). Thus, the neuron-specific association of major extracellular matrix constituents appears to be a part of the

Conclusions

The data presented demonstrate that the PNs of extracellular matrix ensheath distinct subpopulations of neurons within the heterogeneous group of non-cholinergic neurons in the primate basal forebrain. The results support the assumption that PNs may not only influence neuronal activity but may, by their absence, contribute to the relatively high susceptibility to injury of the neurons of the cholinergic basal nucleus of Meynert complex and its extensive degeneration in Alzheimer’s disease.

Acknowledgements

The authors thank Mrs. Margit Schmidt for expert technical assistance. This work was partly supported by the Bundesministerium für Bildung, Forschung und Technologie (BMBF), Interdisciplinary Centre for Clinical Research at the University of Leipzig (01KS9504, Project C1).

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Perineuronal nets in the rhesus monkey and human basal forebrain including basal ganglia

Abstract

Section snippets

Tissue preparation

Staining of extracellular matrix components in the rhesus monkey and human brain tissue

Discussion

Conclusions

Acknowledgements

Neuroscience

Neurobiol. Dis.

Neurobiol. Dis.

J. Neurol. Sci.

Prog. Neurobiol.

Brain Res.

Brain Res.

Neuroscience

J. Chem. Neuroanat.

Cell Calcium

Brain Res. Rev.

Trends Neurosci.

Neurobiol. Aging

Lancet

Prog. Neurobiol.

Exp. Neurol.

Neuroscience

Brain Res.

Neuroscience

Brain Res.

Brain Res.

J. Chem. Neuroanat.

Trends Neurosci.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Semin. Neurosci.

Neuroscience

Trends Neurosci.

Brain Res.

Prog. Neurobiol.

Neurosci. Res.

Neuroscience

Neuroscience

Exp. Neurol.

Brain Res.

Brain Res.

Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s disease

Acta Neuropathol.

Cortical load of PHF-tau in Alzheimer’s disease is correlated to cholinergic dysfunction

J. Neural Transm.

Chondroitin sulfate proteoglycan surrounds a subset of human and rat CNS neurons

J. Neurosci. Res.

Co-occurrence of perineuronal nets with GABAA receptor alpha 1 subunit-immunoreactive neurones in the rat septal region

NeuroReport

Two distinct populations of cholinergic neurons in the septum of raccoon (Procyon lotor): evidence for a separate subset in the lateral septum

J. Comp. Neurol.

Perineuronal nets provide a polyanionic, glia-associated form of microenvironment around certain neurons in many parts of the rat brain

Glia

Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R

J. Comp. Neurol.

Co-occurrence of perineuronal nets with GABA_A receptor alpha 1 subunit-immunoreactive neurones in the rat septal region