{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:37:44Z","timestamp":1760189864952,"version":"build-2065373602"},"reference-count":101,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.<\/jats:p>","DOI":"10.3390\/biology13030155","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T06:14:22Z","timestamp":1709100862000},"page":"155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Aging and Nerve Growth Factor on Neuropeptide Expression and Cholinergic Innervation of the Rat Basolateral Amygdala"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-3143","authenticated-orcid":false,"given":"Pedro A.","family":"Pereira","sequence":"first","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Marta","family":"Tavares","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2834-884X","authenticated-orcid":false,"given":"Miguel","family":"Laires","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-7247","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Mota","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0721-6547","authenticated-orcid":false,"given":"Maria Dulce","family":"Madeira","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Manuel M.","family":"Paula-Barbosa","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2967-6990","authenticated-orcid":false,"given":"Armando","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.arr.2015.09.005","article-title":"Successful aging: Advancing the science of physical independence in older adults","volume":"24","author":"Anton","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.neubiorev.2019.01.003","article-title":"Neurochemical changes in the aging brain: A systematic review","volume":"98","author":"Cleeland","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1474-9726.2007.00289.x","article-title":"Changes in the structural complexity of the aged brain","volume":"6","author":"Dickstein","year":"2007","journal-title":"Aging Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neurobiolaging.2019.04.016","article-title":"What are the threats to successful brain and cognitive aging?","volume":"89","author":"Gallagher","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrn3256","article-title":"The cognitive neuroscience of ageing","volume":"13","author":"Grady","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/jnc.14037","article-title":"Brain aging and neurodegeneration: From a mitochondrial point of view","volume":"143","author":"Grimm","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.cmet.2018.05.011","article-title":"Hallmarks of brain aging: Adaptive and pathological modification by metabolic states","volume":"2018","author":"Mattson","year":"2018","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1126\/science.7046051","article-title":"The cholinergic hypothesis of geriatric memory dysfunction","volume":"217","author":"Bartus","year":"1982","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1097\/WNR.0b013e32800fef5a","article-title":"Aging causes partial loss of basal forebrain but no loss of pontine reticular cholinergic neurons","volume":"17","author":"Baskerville","year":"2006","journal-title":"Neuroreport"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/329065a0","article-title":"Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor","volume":"329","author":"Fischer","year":"1987","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0197-4580(01)00345-1","article-title":"Amelioration of cholinergic neurons dysfunction in aged rats depends on the continuous supply of NGF","volume":"23","author":"Niewiadomska","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1016\/j.neurobiolaging.2013.02.011","article-title":"Nerve growth factor retrieves neuropeptide Y and cholinergic immunoreactivity in the nucleus accumbens of old rats","volume":"34","author":"Pereira","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.bbr.2010.11.058","article-title":"The cholinergic system in aging and neuronal degeneration","volume":"221","author":"Schliebs","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"654931","DOI":"10.3389\/fnagi.2021.654931","article-title":"The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain","volume":"13","author":"Gasiorowska","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41583-023-00677-x","article-title":"Basal forebrain cholinergic signalling: Development, connectivity and roles in cognition","volume":"24","author":"Ananth","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103608","DOI":"10.1016\/j.concog.2023.103608","article-title":"Acetylcholine and metacognition during sleep","volume":"117","author":"Gott","year":"2024","journal-title":"Conscious. Cogn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.neubiorev.2003.09.003","article-title":"The medial prefrontal cortex in the rat: Evidence for a dorso-ventral distinction based upon functional and anatomical characteristics","volume":"27","author":"Heidbreder","year":"2003","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.nlm.2016.06.001","article-title":"The role of basal forebrain cholinergic neurons in fear and extinction memory","volume":"133","author":"Knox","year":"2016","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.neuroscience.2004.03.005","article-title":"Basal forebrain neurons modulate the synthesis and expression of neuropeptides in the rat suprachiasmatic nucleus","volume":"125","author":"Madeira","year":"2004","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00702-016-1530-9","article-title":"Structural and functional considerations of the cholinergic brainstem","volume":"123","year":"2016","journal-title":"J. Neural Transm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/(SICI)1096-9861(19970915)386:1<46::AID-CNE6>3.0.CO;2-D","article-title":"Selective changes in hippocampal neuropeptide Y neurons following removal of the cholinergic septal inputs","volume":"386","author":"Milner","year":"1997","journal-title":"J. Comp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.neuroscience.2014.10.054","article-title":"Lesions of the laterodorsal tegmental nucleus alter the cholinergic innervation and neuropeptide Y expression in the medial prefrontal cortex and nucleus accumbens","volume":"284","author":"Pereira","year":"2015","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.bbr.2009.12.046","article-title":"Cholinergic systems mediate action from movement to higher consciousness","volume":"221","author":"Woolf","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0006-8993(98)00484-3","article-title":"Selective lesion of the cholinergic basal forebrain causes a loss of cortical neuropeptide Y and somatostatin neurons","volume":"800","author":"Zhang","year":"1998","journal-title":"Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neuint.2018.02.003","article-title":"Cholinergic tone in ventral tegmental area: Functional organization and behavioral implications","volume":"114","author":"Zhang","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/0306-4522(83)90108-2","article-title":"Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1\u2013Ch6)","volume":"10","author":"Mesulam","year":"1983","journal-title":"Neuroscience"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3389\/fnins.2019.00129","article-title":"ProNGF and Neurodegeneration in Alzheimer\u2019s Disease","volume":"13","author":"Fahnestock","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1146\/annurev.neuro.24.1.1217","article-title":"Nerve growth factor signaling, neuroprotection, and neural repair","volume":"24","author":"Sofroniew","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.neurobiolaging.2011.09.031","article-title":"Cortical peroxynitration of nerve growth factor in aged and cognitively impaired rats","volume":"33","author":"Bruno","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kropf, E., and Fahnestock, M. (2021). Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10081983"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/cne.902340203","article-title":"Cholinergic projections from the basal forebrain to the basolateral amygdaloid complex: A combined retrograde fluorescent and immunohistochemical study","volume":"234","author":"Carlsen","year":"1985","journal-title":"J. Comp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0306-4522(94)90252-6","article-title":"Two types of cholinergic projections to the rat amygdala","volume":"60","author":"Heckers","year":"1994","journal-title":"Neuroscience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1523\/JNEUROSCI.14-03-01271.1994","article-title":"Complete and selective cholinergic de-nervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor","volume":"14","author":"Heckers","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/cne.902490405","article-title":"The distribution of choline acetyltransferase in the rat amygdaloid complex and adjacent cortical areas, as determined by quantitative micro-assay and immunohistochemistry","volume":"249","author":"Hellendall","year":"1986","journal-title":"J. Comp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1523\/JNEUROSCI.02-04-00513.1982","article-title":"Cholinergic projections from the basal forebrain of rat to the amygdala","volume":"2","author":"Nagai","year":"1982","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.5607\/en.2019.28.3.320","article-title":"Basal Forebrain Cholinergic-induced Activation of Cholecystokinin Inhibitory Neurons in the Basolateral Amygdala","volume":"28","author":"Lee","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0301-0082(98)00003-3","article-title":"Cortical pathways to the mammalian amygdala","volume":"55","author":"McDonald","year":"1998","journal-title":"Prog. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-815134-1.00001-5","article-title":"Functional neuroanatomy of the basolateral amygdala: Neurons, neurotransmitters, and circuits","volume":"26","author":"McDonald","year":"2020","journal-title":"Handb. Behav. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1152\/physrev.00002.2003","article-title":"The amygdaloid complex: Anatomy and physiology","volume":"83","author":"Sah","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/7854_2009_7","article-title":"Neuroanatomy of anxiety","volume":"2","author":"Canteras","year":"2010","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nature14188","article-title":"From circuits to behaviour in the amygdala","volume":"517","author":"Janak","year":"2015","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainres.2009.03.038","article-title":"Brain stress systems in the amygdala and addiction","volume":"1293","author":"Koob","year":"2009","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fnbeh.2014.00107","article-title":"Optogenetic dissection of amygdala functioning","volume":"8","author":"Lalumiere","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"633235","DOI":"10.3389\/fncir.2021.633235","article-title":"Inhibitory Circuits in the Basolateral Amygdala in Aversive Learning and Memory","volume":"15","author":"Perumal","year":"2021","journal-title":"Front. Neural Circuits"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"656944","DOI":"10.3389\/fnagi.2021.656944","article-title":"Age-related memory impairment and sex-specific alterations in phosphorylation of the Rpt6 proteasome subunit and polyubiquitination in the basolateral amygdala and medial prefrontal cortex","volume":"13","author":"Dulka","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neurobiolaging.2007.05.006","article-title":"Age-related dendritic hypertrophy and sexual dimorphism in rat basolateral amygdala","volume":"30","author":"Rubinow","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Amado, M., and Prensa, L. (2012). Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex. PLoS ONE, 7.","DOI":"10.1371\/annotation\/42d5754a-295b-466e-ae55-6f9f41b06760"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"687257","DOI":"10.3389\/fncir.2021.687257","article-title":"Interneuron Types and Their Circuits in the Basolateral Amygdala","volume":"15","year":"2021","journal-title":"Front. Neural Circuits"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.neuropharm.2010.11.006","article-title":"Interneurons in the basolateral amygdala","volume":"60","author":"Spampanato","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/cne.22550","article-title":"Cholinergic innervation of pyramidal cells and parvalbumin-immunoreactive interneurons in the rat basolateral amygdala","volume":"519","author":"Muller","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.npep.2013.10.012","article-title":"Neuropeptides in learning and memory","volume":"47","author":"Scheich","year":"2013","journal-title":"Neuropeptides"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.expneurol.2012.09.004","article-title":"Neuropeptide Y and its role in CNS disease and repair","volume":"238","author":"Decressac","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.smrv.2009.09.001","article-title":"Neuropeptide Y and sleep","volume":"14","author":"Dyzma","year":"2010","journal-title":"Sleep. Med. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lim, R., and Lajtha, A. (2006). Handbook of Neurochemistry and Molecular Neurobiology, Neuroactive Proteins and Peptides, Springer.","DOI":"10.1007\/978-0-387-30381-9"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lim, R., and Lajtha, A. (2006). Handbook of Neurochemistry and Molecular Neurobiology, Neuroactive Proteins and Peptides, Springer.","DOI":"10.1007\/978-0-387-30381-9"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1023\/B:NEUR.0000046575.32270.e6","article-title":"The effects of nerve growth factor upon the neuropeptide content of the suprachiasmatic nucleus of rats withdrawn from ethanol are mediated by the nucleus basalis magnocellularis","volume":"33","author":"Pereira","year":"2004","journal-title":"J. Neurocytol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.neuroscience.2005.10.027","article-title":"Reduced density of neuropeptide Y neurons in the somatosensory cortex of old male and female rats: Relation to cholinergic depletion and recovery after nerve growth factor treatment","volume":"137","author":"Cardoso","year":"2006","journal-title":"Neuroscience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9737","DOI":"10.1007\/s11357-014-9737-x","article-title":"Old-onset caloric restriction effects on neuropeptide Y- and somatostatin-containing neurons and on cholinergic varicosities in the rat hippocampal formation","volume":"36","author":"Cardoso","year":"2014","journal-title":"Age"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.brainres.2005.04.066","article-title":"Nerve growth factor restores the expression of vasopressin and vasoactive intestinal polypeptide in the suprachiasmatic nucleus of aged rats","volume":"1048","author":"Pereira","year":"2005","journal-title":"Brain Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.exger.2016.09.017","article-title":"Nerve growth factor-induced plasticity in medial prefrontal cortex interneurons of aged Wistar rats","volume":"85","author":"Pereira","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1023\/A:1012745606781","article-title":"Nerve growth factor restores mRNA levels and the expression of neuropeptides in the suprachiasmatic nucleus of rats submitted to chronic ethanol treatment and withdrawal","volume":"30","author":"Silva","year":"2001","journal-title":"J. Neurocytol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0006-8993(03)03030-0","article-title":"NGF and NT-3 exert differential effects on the expression of neuropeptides in the suprachiasmatic nucleus of rats withdrawn from ethanol treatment","volume":"983","author":"Pereira","year":"2003","journal-title":"Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0306-4522(03)00205-7","article-title":"Nerve growth factor prevents cell death and induces hypertrophy of basal forebrain cholinergic neurons in rats withdrawn from prolonged ethanol intake","volume":"119","author":"Pereira","year":"2003","journal-title":"Neuroscience"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1111\/j.1471-4159.2004.02575.x","article-title":"Effects of post-injury hypothermia and nerve growth factor infusion on antioxidant enzyme activity in the rat: Implications for clinical therapies","volume":"90","author":"DeKosky","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s00221-002-1290-7","article-title":"Nerve growth factor improves spatial learning and restores hippocampal cholinergic fibers in rats withdrawn from chronic treatment with ethanol","volume":"148","author":"Lukoyanov","year":"2003","journal-title":"Exp. Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/j.1471-4159.1990.tb04594.x","article-title":"Exogenous nerve growth factor increases the activity of high-affinity choline uptake and choline acetyltransferase in brain of Fisher 344 male rats","volume":"55","author":"Williams","year":"1990","journal-title":"J. Neurochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.neuro.2016.04.007","article-title":"Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus","volume":"54","author":"Pereira","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_68","unstructured":"Paxinos, G., and Watson, C. (1998). The Rat Brain in Stereotaxic Coordinates, Academic Press. [4th ed.]."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1365-2818.1987.tb02837.x","article-title":"The efficiency of systematic sampling in stereology and its prediction","volume":"147","author":"Gundersen","year":"1987","journal-title":"J. Microsc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1046\/j.1365-2818.1999.00457.x","article-title":"The efficiency of systematic sampling in stereology\u2014Reconsidered","volume":"193","author":"Gundersen","year":"1999","journal-title":"J. Microsc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.brainres.2004.07.013","article-title":"Timed hypocaloric food restriction alters the synthesis and expression of vasopressin and vasoactive intestinal peptide in the suprachiasmatic nucleus","volume":"1022","author":"Andrade","year":"2004","journal-title":"Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1523\/JNEUROSCI.19-07-02706.1999","article-title":"Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes","volume":"19","author":"Wong","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/cne.21924","article-title":"Neuron and glia numbers in the basolateral nucleus of the amygdala from preweaning through old age in male and female rats: A stereological study","volume":"512","author":"Rubinow","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2174\/138920311795906718","article-title":"Aging and peptide control of food intake","volume":"12","author":"Kmiec","year":"2011","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1210\/endo.137.10.8828508","article-title":"Fasting-induced increases in food intake and neuropeptide Y gene expression are attenuated in aging male Brown Norway rats","volume":"137","author":"Gruenewald","year":"1996","journal-title":"Endocrinology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1210\/endo.143.3.8670","article-title":"Testosterone (T)-induced changes in arcuate nucleus cocaine-amphetamine regulated transcript and NPY mRNA are attenuated in old compared to young male Brown Norway rats: Contribution of T to age related changes in cocaine amphetamine-regulated transcript and NPY gene expression","volume":"143","author":"Sohn","year":"2002","journal-title":"Endocrinology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0531-5565(01)00233-9","article-title":"Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression","volume":"37","author":"Marck","year":"2002","journal-title":"Exp. Gerontol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/(SICI)1096-9861(19980504)394:2<252::AID-CNE9>3.0.CO;2-1","article-title":"Hippocampal interneurons expressing glutamic acid decarboxylase and calcium-binding proteins decrease with aging in Fischer 344 rats","volume":"394","author":"Shetty","year":"1998","journal-title":"J. Comp. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0065-1281(11)80354-5","article-title":"Histo- and immunohistochemical changes in acetylcholinesterase and choline acetyltransferase activities in the amygdaloid complex in aged rats","volume":"89","author":"Lolova","year":"1990","journal-title":"Acta Histochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/cne.903360110","article-title":"Cholinergic innervation of the amygdaloid complex in the human brain and its alterations in old age and Alzheimer\u2019s disease","volume":"336","author":"Emre","year":"1993","journal-title":"J. Comp. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.neurobiolaging.2010.10.011","article-title":"Correlation of cognitive performance and morphological changes in neocortical pyramidal neurons in aging","volume":"33","author":"Allard","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/cne.23863","article-title":"Age effects on the nucleus of the lateral olfactory tract of the rat","volume":"524","author":"Vaz","year":"2016","journal-title":"J. Comp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"111298","DOI":"10.1016\/j.exger.2021.111298","article-title":"Effects of aging on the cholinergic innervation of the rat ventral tegmental area: A stereological study","volume":"148","author":"Pereira","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0079-6123(03)45004-8","article-title":"The cholinergic innervation of the human cerebral cortex","volume":"145","author":"Mesulam","year":"2004","journal-title":"Prog. Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1073\/pnas.89.7.2639","article-title":"Nerve growth factor-induced synaptogenesis and hypertrophy of cortical cholinergic terminals","volume":"89","author":"Garofalo","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2006.03695.x","article-title":"The \u201cins\u201d and \u201couts\u201d of the high-affinity choline transporter CHT1","volume":"97","author":"Ribeiro","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrn1588","article-title":"Choline transporters, cholinergic transmission and cognition","volume":"6","author":"Sarter","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0047-6374(89)90005-5","article-title":"Effect of aging and acetyl-Lcarnitine on energetic and cholinergic metabolism in rat brain regions","volume":"47","author":"Curti","year":"1989","journal-title":"Mech. Ageing Dev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/0006-8993(92)90601-5","article-title":"Decreased [3H]hemicholinium binding to high-affinity choline uptake sites in aged rat brain","volume":"570","author":"Forloni","year":"1992","journal-title":"Brain Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/0736-5748(90)90063-8","article-title":"Pre- and post-synaptic cholinergic dysfunction in aged rodent brain regions: New findings and an interpretative review","volume":"8","author":"Sherman","year":"1990","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0197-4580(81)90006-3","article-title":"Presynaptic cholinergic mechanisms in brain of aged rats with memory impairments","volume":"2","author":"Sherman","year":"1981","journal-title":"Neurobiol. Aging"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1254\/jjp.66.247","article-title":"Age-related changes of cholinergic markers in the rat brain","volume":"66","author":"Yufu","year":"1994","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0047-6374(94)01539-X","article-title":"In situ determination of M1 and M2 muscarinic receptor binding sites and mRNAs in young and old rat brains","volume":"78","author":"Narang","year":"1995","journal-title":"Mech. Ageing Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.peptides.2007.11.001","article-title":"Cholinergic regulation of neuropeptide Y synthesis and release in human neuroblastoma cells","volume":"29","author":"Dozio","year":"2008","journal-title":"Peptides"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0006-8993(98)00471-5","article-title":"Cholinergic muscarinic mechanisms regulate neuropeptide Y gene expression via protein kinase C in human neuroblastoma cells","volume":"798","author":"Magni","year":"1998","journal-title":"Brain Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/cne.903500407","article-title":"TrkA-immunoreactive profiles in the central nervous system: Colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin","volume":"350","author":"Sobreviela","year":"1994","journal-title":"J. Comp. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0306-4522(90)90304-M","article-title":"Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system\u2014I. Forebrain","volume":"34","author":"Pioro","year":"1990","journal-title":"Neuroscience"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5131","DOI":"10.1523\/JNEUROSCI.15-12-08131.1995","article-title":"Nerve growth factor facilitates cholinergic neurotransmission between nucleus basalis and the amygdala in rat: An electrophysiological analysis","volume":"15","author":"Moises","year":"1995","journal-title":"J. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.neuroscience.2009.02.077","article-title":"Parvalbumin-immunoreactive neurons and GABAergic neurons of the basal forebrain project to the rat basolateral amygdala","volume":"160","author":"Mascagni","year":"2009","journal-title":"Neuroscience"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1523\/JNEUROSCI.4957-04.2005","article-title":"Nerve growth factor rapidly increases muscarinic tone in mouse medial septum\/diagonal band of Broca","volume":"25","author":"Wu","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"21100","DOI":"10.1074\/jbc.271.35.21100","article-title":"Neurotrophins stimulate the release of dopamine from rat mesencephalic neurons via Trk and p75Lntr receptors","volume":"271","author":"Sirrenberg","year":"1996","journal-title":"J. Biol. Chem."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/3\/155\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:06:23Z","timestamp":1760105183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/3\/155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,28]]},"references-count":101,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["biology13030155"],"URL":"https:\/\/doi.org\/10.3390\/biology13030155","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2024,2,28]]}}}