Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites

Araujo, Dalia M.; Lapchak, Paul A.; Meaney, M.J.; Collier, B.; Quirion, Rémi

doi:10.1523/jneurosci.10-09-03069.1990

Cited by 146 publications

(45 citation statements)

References 56 publications

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“…However, a decrease in M2 binding with aging has been reported in other strains (Biegon et aI. , 1989;Araujo et aI., 1990), whereas M 1 receptor seems to be less susceptible to the effects of age (Araujo et al , 1990). Reduction of M2 binding was observed in some of the regions where the effects of THA are no longer found in our experiment.…”

Section: Effect Of Thasupporting

confidence: 51%

Metabolic Response to Tacrine (THA) and Physostigmine in the Aged Rat Brain

Bassant

Jazat-Poindessous

Lamour

1995

J Cereb Blood Flow Metab

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Summary: The effects of the centrally acting anti cholinesterases tacrine (tetrahydroaminoacridine, THA) and physostigmine (PHY), on local cerebral glucose uti lization (LCGU) have been studied in 27-month-old rats, using the autoradiographic e4Cjdeoxyglucose technique. THA (10 mg/kg i.p.) increased LCGU significantly in 13 of the 54 regions studied (24%) including insular, parietal, temporal, and retrosplenial cortices, septohippocampal system, thalamus, lateral habenula, and superior collicu Ius. In these regions, the average THA-induced increase in LCGU was 24% above control. The whole brain mean LCGU was not significantly increased. PHY (0. 5 mg/kg) increased LCGU in 18% of the regions (average eleva tion, 23%). The whole brain mean LCGU increased byThe centrally acting cholinesterase inhibitor tet rahydroaminoacridine (THA, tacrine) has been re ported to improve cognitive deficits in subpopula tions of Alzheimer's disease (AD) patients. Several multicenter studies (Eagger et aI., 1991; Davis et aI. , 1992; Farlow et aI., 1992; Knapp et aI., 1994) have confirmed the initial positive results of Sum mers (S ummers et aI., 1986). The effects of THA in mildly demented AD patients persist during long term treatment and indicate that THA might not only act on symptoms but also delay the disease process (Nordberg et aI., 1992). The mechanisms mediating the effects of THA are far from clear, but experimental data indicate that THA may produce its therapeutic effects, at least in part, via its action on cholinergic transmission (for review, see Free man and Dawson, 1991). In experimental animals, 1093 7% (p < 0.05). The regional distributions of THA-and PHY-induced increases in LCGU were extremely similar and overlapped the distribution of the M2 muscarinic re ceptors and that of acetylcholinesterase activity, suggest ing that the major effects of THA and PHY on LCGU result from their anticholinesterase action. As compared to those of 3-month-old rats, both the number of regions affected and the amplitude of the metabolic activation were significantly less in aged rats. However, the drugs were still active in old rats and compensated for the age related hypometabolism in some brain areas.

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Section: Effect Of Thasupporting

confidence: 51%

Metabolic Response to Tacrine (THA) and Physostigmine in the Aged Rat Brain

Bassant

Jazat-Poindessous

Lamour

1995

J Cereb Blood Flow Metab

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“…Aged rats showed a decreased sensitivity to nicotine, and a greatly decreased maximal effect of nicotine on the ability to increase cortical cerebral blood flow (Uchida et al, 1997). In addition, nicotine-elicited dopamine release was significantly decreased in the striatum of aged rats, both in vivo and in vitro (Schulz et al, 1993;Okamoto et al, 1994), whereas ACh release elicited by the nicotinic agonist methyl-carbamylcholine was decreased in frontal cortical and hippocampal slices (Araujo et al, 1990).…”

Section: Cholinergic Hypothesis Of Brain Aging: Studies Of Nachr Exprmentioning

confidence: 99%

Nicotinic receptors in aging and dementia

2002

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Activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been shown to maintain cognitive function following aging or the development of dementia. Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects. Smoking has also been shown in some epidemiological studies to be protective against the development of neurodegenerative diseases. This is supported by animal studies that have shown nicotine to be neuroprotective both in vivo and in vitro. Treatment with nicotinic agonists may therefore be useful in both slowing the progression of neurodegenerative illnesses, and improving function in patients with the disease. While increased nicotinic function has been shown to be beneficial, loss of cholinergic markers is often seen in patients with dementia, suggesting that decreased cholinergic function could contribute to both the cognitive deficits, and perhaps the neuronal degeneration, associated with dementia. In this article we will review the literature on each of these areas. We will also present hypotheses that might address the mechanisms underlying the ability of nAChR function to protect against neurodegeneration or improve cognition, two potentially distinct actions of nicotine.

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“…Age-dependent morphological and physiological changes within the cholinergic system of the brain have been described as a major mechanism underlying impairments of learning and memory (2,3). Numerous studies in aged rats have revealed that a degeneration of cholinergic neurons in the basal forebrain is associated with learning and >memory deficits (4).…”

Section: Senktide | In Vivo Microdialysismentioning

confidence: 99%

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Silva

Lenz

Rotter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism. senktide | in vivo microdialysis H umans exhibit a decline in cognitive capacity with age, which may progressively lead to dementia (1). Age-dependent morphological and physiological changes within the cholinergic system of the brain have been described as a major mechanism underlying impairments of learning and memory (2, 3). Numerous studies in aged rats have revealed that a degeneration of cholinergic neurons in the basal forebrain is associated with learning and >memory deficits (4). Likewise, the consistent correlations found between cholinergic degeneration and cognitive impairments indicate a high correspondence between acetylcholinergic activity and the magnitude of cognitive decline (4-6). This relationship has also been shown in patients with Alzheimer's disease (7,8).The neuropeptide neurokinins (NKs) substance P, neurokinin A, neurokinin B (NK-B), neuropeptide K, neuropeptide γ, and hemokinin 1 bind to the three known NK-receptors (NK3-R) (NK1-, NK2-, and NK3-R) with different degrees of affinity, whereby NK-B is the preferred ligand to NK3-R (9). NK3-Rs are widespread in the brain, including areas that are implicated in processes governing learning and memory such as the hippocampus, frontal cortex (FC), and medial septum (10, 11). There is a close interaction between NK3-R and the cholinergic system. NK3-R are localized on cholinacetyltransferase-containing neurons in ...

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Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites

Cited by 146 publications

References 56 publications

Metabolic Response to Tacrine (THA) and Physostigmine in the Aged Rat Brain

Metabolic Response to Tacrine (THA) and Physostigmine in the Aged Rat Brain

Nicotinic receptors in aging and dementia

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

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