The role of neuropeptides in learning: focus on the neurokinin substance P

Huston, Joseph P.; Hasenöhrl, Rüdiger U.

doi:10.1016/0166-4328(94)00132-y

Cited by 134 publications

(74 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of the cognitively important proline-specific neuropeptides are believed to be degraded by PEP (Amor et al, 2004;Diderot et al, 2005;Huston & Hasenohrl, 1995). Various authors have reported an unusually higher PEP levels in the patients suffering from AD and suggested that PEP might be one of the several factors involved in cognitive decline associated with aging (Lee & Paik, 2003;Tezuka et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichenCetrelia olivetorum

Savale

Pol

Khare

et al. 2015

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Lichens are source of natural bioactive compounds which are traditionally used to cure a variety of ailments. Objective: The objective of this study is to assess free radical scavenging, prolyl endopeptidase inhibitory (PEPI), and antimicrobial potential of a high altitude lichen species Cetrelia olivetorum (Nyl.) W. L. Culb. & C. F. Culb (Parmeliaceae). Materials and methods: Lichen C. olivetorum has been cultured in vitro, and optimized culture conditions were implemented in bioreactor to obtain high quantity of biomass for the study of radical scavenging, PEPI, and antimicrobial activities. Radical scavenging activity of methanol extract of Cetrelia olivetorum (MECO) was tested at 100 mg/mL, PEPI activity at 25 and 50 mg/mL, and antimicrobial activity at 5, 25, 50, and 100 mg/mL conc. All the biological activities of natural thallus extract and its derived culture extract were evaluated spectrophotometrically. Results: Murashige and Skoog medium supplemented with 3% glucose and 100 ppb indole-3-butyric acid (IBA) supported biomass growth at flask level and yielded 5.095 g biomass in bioreactor. MECO of both the cultured and the natural lichen exhibited half inhibiting concentration (IC 50 ) for radical scavenging activities in the range of 50-60 mg/mL, whereas the IC 50 value of standard antioxidants was found to be in the range of 12-29 mg/mL. The IC 50 value of lichen extract for PEPI activity was 144-288 mg/mL, whereas the IC 50 value of standard prolyl endopeptidase inhibitor, Z-pro-prolinal, was 57.73 mg/mL. As far as the antimicrobial activity of MECO is concerned, minimum inhibitory concentration (MIC) value of lichen extracts against tested microorganisms was obtained in the range of 50-104 mg/mL and found to be more effective than commercially available standard erythromycin. Discussion: Murashige and Skoog medium containing IBA was found to be suitable for maximum biomass production of C. olivetorum under bioreactor conditions. The cultured lichen biomass extract also showed antioxidant, PEPI, and antimicrobial potential. Conclusion: The present study indicates therapeutic potential of Himalayan lichen C. olivetorum against neurodegenerative diseases owing to its radical scavenging, PEPI, and antimicrobial activities. Further, the result encourages its commercial exploitation through mass culture for production of its bioactive components and their use in pharmaceutical and nutraceutical industries.

show abstract

Section: Introductionmentioning

confidence: 99%

Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichenCetrelia olivetorum

Savale

Pol

Khare

et al. 2015

Pharmaceutical Biology

View full text Add to dashboard Cite

show abstract

“…Several neuropeptides, particularly substance P, have been implicated in learning and memory (Huston and Hasenohrl 1995) and are present endogenously in cortex and striatum. Substance P levels are also depleted in the striatum of monkeys made parkinsonian by exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).…”

mentioning

confidence: 99%

Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys

Schneider

2002

Neuropsychopharmacology

View full text Add to dashboard Cite

A number of neuropeptides are affected in Parkinson's disease and the enzyme proline endopeptidase contributes to the degradation of many of these neuropeptides, some of which are linked to a variety of cognitive functions. In the present study, the effects of the highly potent proline endopeptidase inhibitor S 17092 on cognitive deficits in monkeys induced by chronic low dose 2,3, It is generally recognized that non-demented Parkinson's disease (PD) patients exhibit a number of neuropsychological deficits, some of which are present even at the earliest stages of the disease (Lees and Smith 1983;Levin et al. 1989;Owen et al. 1993). Many of these deficits are 'frontal-like' in nature and consist of problems in attentional set shifting (Owen et al. 1993), distractibility (Sharpe 1990) planning and 'executive functions ' (Morris et al. 1988) and spatial working memory ). Parkinson's disease patients also may have difficulty performing a delayed matching-to-sample shortterm visual recognition memory task, but their problems appear more related to attentional difficulties rather than to visual recognition memory problems . The neurochemical deficits underlying the cognitive disturbances in PD patients are not completely known. While most of the motor symptoms of PD can be related to a nigrostriatal dopaminergic defect, the relationship between the dopaminergic defect and cognitive deficits in PD is less clear. Some cognitive deficits in PD may be dopa-responsive but others are not (Cooper et al. 1992;Lange et al. 1992). Some cognitive problems in PD patients are even exacerbated by dopaminergic therapy (Gotham et al. 1988). These findings suggest that the cognitive deficits in PD patients most likely arise from dysfunction of several cortical and subcortical neurotransmitter systems and functional circuits that cannot be normalized by dopamine replacement therapy alone. This is supported by the recent finding that a sub-type specific neuronal nicotinic acetylcholine receptor agonist, but not levodopa, was able to improve cognitive functioning in dopamine lesioned monkeys (Schneider et al. 1999). The nicotinic receptor agonist effects on cognition were most likely related to the ability of this compound to release dopamine from striatal, limbic and frontal cortical sites, norepinephrine from hippocampal, thalamic and frontal cortical sites and acetylcholine from various cortical and subcortical sites (Menzaghi et al. 1996;Sacaan et al. 1997).In addition to deficits in levels of various neurotransmitters in PD and in animal models of PD, decreased levels of various neuropeptides may also contribute to parkinsonian symptomatology (Mauborgne et al. 1983). Several neuropeptides, particularly substance P, have been implicated in learning and memory (Huston and Hasenohrl 1995) and are present endogenously in cortex and striatum. Substance P levels are also depleted in the striatum of monkeys made parkinsonian by exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since proline-containing neuropep...

show abstract

“…Controls received saline 2 ml/kg. memory processes [1,2]. POP plays an important role in the catabolism of proline-containing peptides such as substance P, arginine-vasopressin, thyrotropin-releasing hormone, bradykinin, angiotensin I and II, neurotensin and oxytocin [2,[25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…memory processes [1,2]. POP plays an important role in the catabolism of proline-containing peptides such as substance P, arginine-vasopressin, thyrotropin-releasing hormone, bradykinin, angiotensin I and II, neurotensin and oxytocin [2,[25][26][27][28]. Post-mortem levels of many neuropeptides, including substance P, arginine-vasopressin and neurotensin, are decreased in patients with Alzheimer's disease [5,[29][30][31].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Beneficial Effect of Prolyl Oligopeptidase Inhibition on Spatial Memory in Young but Not in Old Scopolamine‐Treated Rats

Jalkanen¹,

Puttonen²,

Venäläinen³

et al. 2006

Basic Clin Pharma Tox

View full text Add to dashboard Cite

The effects of a novel prolyl oligopeptidase (POP) inhibitor KYP-2047 on spatial memory of young (3-monthold) and old (8-to 9-month-old) scopolamine-treated rats (0.4 mg/kg intraperitoneally) was investigated in the Morris water maze. In addition, the concentrations of promnesic neuropeptide substrates of POP, substance P and neurotensin in various brain areas after acute and chronic POP inhibition were measured in young rats. In addition, inositol-1,4,5-trisphosphate (IP 3 ) levels were assayed in rat cortex and hippocampus after effective 2.5-day POP inhibition. KYP-2047 (1 or 5 mg/kg 30 min. before daily testing) dose-dependently improved the escape performance (i.e. latency to find the hidden platform and swimming path length) of the young but not the old rats in the water maze. POP inhibition had no consistent effect on substance P levels in cortex, hippocampus or hypothalamus, and only a modest increase in neurotensin concentration was observed in the hypothalamus after a single dose of KYP-2047. Moreover, IP 3 concentrations remained unaffected in cortex and hippocampus after POP inhibition. In conclusion, the behavioural data support the earlier findings of the promnesic action of POP inhibitors, but the mechanism of the memory-enhancing action remains unclear.In addition to the cholinergic neurones, many neuropeptides may play a role in cognitive functions such as learning and memory. These peptides include vasopressin, neurotensin, oxytocin, substance P and bradykinin [1,2]. A common feature of the above-mentioned promnesic neuropeptides is their sensitivity to prolyl oligopeptidase (POP, EC 3.4.21.26), also known as prolyl endopeptidase [1]. POP is a member of the serine protease family that hydrolyses peptide bonds at the carboxy terminal of  -proline. The effects of POP in memory disorders are somewhat conflicting. On one hand, some findings suggest that a decrease in POP activity is characteristic of a generalized process of neurodegeneration, including Alzheimer's disease and dementia [3]. However, for example in Alzheimer's disease, the changes in POP activities depend on which brain areas are being investigated. In cerebral cortex, a reduction in POP activity has been observed, whereas in occipital cortex, the POP activity seems to increase [4]. It has been proposed but not proved that these alterations in POP activity in Alzheimer's disease and dementia account for some of the observed changes in neuropeptide levels. In Alzheimer's disease, vasopressin and substance P levels decrease in cortical areas and hippocampus [5], areas implicated in cognitive processes. Furthermore, increased levels of neuropeptides have been shown to improve cognitive function in experimental animals [6,7].These observations would seem to indicate that manipulations of POP activity and its secondary effects on neuropeptide levels could represent a potential therapeutic target for treatment of cognitive disorders. Several POP inhibitors have been studied in animals. Studies with rats have demonstrated memo...

show abstract

The role of neuropeptides in learning: focus on the neurokinin substance P

Cited by 134 publications

References 74 publications

Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichenCetrelia olivetorum

Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichenCetrelia olivetorum

Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys

Beneficial Effect of Prolyl Oligopeptidase Inhibition on Spatial Memory in Young but Not in Old Scopolamine‐Treated Rats

Contact Info

Product

Resources

About