Summary
The neuropeptide galanin is known to inhibit the evoked release of acetylcholine in ventral hippocampus of the rat. Co-localization of this peptide with choline acetyltransferase in neurons of the cholinergic septal nuclei has been demonstrated in the rat and non-human primate. The severe deficiency of the cholinergic hippocampal projection system arising mainly from the vertical limb nucleus of the diagonal band of Broca, also referred to as Ch2 region, is a constant finding in Alzheimer's disease, a disorder which is neuropathologically characterized by the appearance of senile plaques, neurofibrillary tangles and congophilic angiopathy in neo- and archicortical structures. In the present study for the first time galanin immunoreactivity in the human Ch2 region is morphologically investigated and related to the severity of hippocampal plaques and neurofibrillary tangles in Alzheimer's disease. An inverse relationship between decreasing galanin immunoreactivity in the Ch2 region and amounts of senile plaques and neurofibrillary tangles in the hippocampus is indicated. Considering the cholinergic deficiency in Alzheimer's disease as a secondary phenomenon to primary cortical and hippocampal lesions, and realizing the inhibitory effect of galanin upon acetylcholine release in hippocampus, this preliminary study suggests that a decreased galanin immunoreactivity in Ch2 in Alzheimer's disease reflects a possible negative feedback mechanism to a degenerating cholinergic projection system.
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Allen SJ, Dawbarn D, Wilcock GK (1988) Morphometric immunochemical analysis of neurons in the nucleus basalis of Meynert in Alzheimer's disease. Brain Res 454:275–281
Amaral DG, Kurz J (1985) An analysis of the origins of the cholinergic and noncholinergic septal projections to the hippocampal formation of the rat. J Comp Neurol 240:37–59
Bartus RT, Dean III RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–417
Blessed G, Tomlinson BE, Roth M (1968) The association between quantitative measures of dementia and of senile change in the gray matter of elderly subjects. Br J Psychiatry 114:797–811
Chan-Palay V (1988) Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer's and Parkinson's disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol 273:543–557
Collerton D (1986) Cholinergic function and intellectual decline in Alzheimer's disease. Neuroscience 19:1–28
Fisone G, Wu CF, Consolo S, Nordström Ö, Brynne N, Bartfat T, Melander T, Hökfelt T (1987) Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical autoradiographic, in vitro and in vivo studies. Proc Natl Acad Sci USA 84:7339–7343
Henke H, Lang W (1983) Cholinergic enzymes in neocortex, hippocampus and basal forebrain of non-neurological and senile dementia of Alzheimer-type patients. Brain Res 267:281–291
Hsu S-M, Raine L, Fanger H (1981) Use of Avidin-Biotin-Peroxidase Complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Hitochem Cytochem 29:577–580
Kitt CA, Mitchell SJ, DeLong MR, Wainer BH, Price DL (1987) Fiber pathways of basal forebrain cholinergic neurons in monkeys. Brain Res 406:192–206
Marti E, Gibson SJ, Polak JM, Facer P, Springall DR, Van Aswegen G, Aitchison M, Koltzenburg M (1987) Ontogeny of peptide-and amine-containing neurons in motor, sensory, and autonomic regions of rat and human spinal cord,dorsal root ganglia, and rat skin. J Comp Neurol 266:332–359
Melander T, Staines WA (1986) A galanin-peptide coexists in putative cholinergic somata of the septum-basal forebrain complex and in acetylcholinesterase-containing fibers and varicosities within the hippocampus in the owl monkey (aotus trivirgatus). Neurosci Lett 68:17–22
Melander T, Staines WA, Hökfelt T, Rökaeus Å,Eckenstein F, Salvaterra PM, Wainer BH (1985) Galanin-like immunoreactivity in cholinergic neurons of the septumbasal forebrain complex projecting to the hippocampus of the rat. Brain Res 360:130–138
Melander T, Staines WA, Rökaeus Å (1986) Galanin-like immunoreactivity in hippocampal afferents in the rat, with special reference to cholinergic and noradrenergic inputs. Neuroscience 19:223–240
Melander T, Hökfelt T, Rökaeus Å (1986) Distribution of galanin-like immunoreactivity in the rat central nervous system. J Comp Neurol 248:475–517
Mesulam M-M, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the Rhesus monkey. J Comp Neurol 214:170–197
Mesulam M-M, Mufson EJ, Wainer BH, Levey AI (1983) Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1–Ch6). Neuroscience 10:1185–1201
Pearson RCA, Sofroniew MV, Cuello AC, Powell TPS, Eckenstein F, Esiri MM, Wilcock GK (1983) Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer's type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Res 289:375–379
Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2:1457–1459
Puchtler H, Sweat F (1965) Congo red as a stain for fluorescence microscopy of amyloid. J Histochem Cytochem 13:693–694
Puchtler H, Sweat F, Levine M (1962) On the binding of Congo red by amyloid. J Histochem Cytochem 10:355–364
Rökaeus Å, Melander T, Hökfelt T, Lundberg JM, Tatemoto K, Carlquist M, Mutt V (1984) A galanin-like peptide in the central nervous system and intestine of the rat. Neurosci Lett 47:161–166
Rye DB, Wainer BH, Mesulam MM, Mufson EB, Saper CB (1984) Cortical projections arising from the basal forebrain: a study of cholinergic and nonchomergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience 13:627–643
Rylett RJ, Ball MJ, Colhoun EH (1983) Evidence for highaffinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's Disease. Brain Res 289:169–195
Skofitsch G, Jacobowitz DM (1985) Immunohistochemical mapping of galanin-like neurons in the rat central nervous system. Peptides 6:509–546
Straus W (1982) Imidazole increases the sensitivity of the cytochemical reaction for peroxidase with diaminobenzidine at a neutral pH. J Histochem Cytochem 30:491–493
Tatemoto K, Rökaeus Å, Jörnvall H, McDonald TJ, Mutt V (1983) Galanin — a novel biologically active peptide from porcine intestine. FEBS Lett 164:124–128
Vogels OJM, ter Laak HJ, Broere CAJ, ten Donkelaar HJ, Nieuwenhuys R, Schulte BPM (1989) Cell loss or shrinkage in the nucleus basalis Meynert complex in Alzheimer's Disease? Neurobiol Aging (in press)
Walker LC, Koliatsost VE, Kitt CA, Richardson RT, Price DL (1987) Galanin-containing somata in the primate nucleus basalis/diagonal band complex. Neuroscience [Abstr] 273:13
Woolf NJ, Butcher LL (1984) Cholinergic systems in the rat brain. I. Projections to the limbic telencephalon. Brain Res Bull 13:751–784
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Vogels, O.J.M., Renkawek, K., Broere, C.A.J. et al. Galanin-like immunoreactivity within Ch2 neurons in the vertical limb of the diagonal band of Broca in aging and Alzheimer's disease. Acta Neuropathol 78, 90–95 (1989). https://doi.org/10.1007/BF00687407
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DOI: https://doi.org/10.1007/BF00687407