Neurokinin-1 expression and co-localization with glutamate and GABA in the hypothalamus of the cat

Yao, Ruihong; Rameshwar, Pranela; Donnelly, Robert; Siegel, Allan

doi:10.1016/s0169-328x(99)00173-4

Cited by 23 publications

(8 citation statements)

References 25 publications

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“…Following middle cerebral artery occlusion, there is a marked expression of substance P and NK 1 receptors in glutamatergic pyramidal cells [92]. Such colocalisation of NMDA and NK 1 receptors had previously been reported in spinal cord [98] and brain [99]. Moreover, this colocalisation may facilitate glutamate-mediated neurotoxicity, a hypothesis supported by the observation that substance P potentiates cellular responses to NMDA, an effect that can be blocked by substance P antagonists [100] and has been implicated in the modulation of locomotor behaviour.…”

Section: Substance P Antagonistssupporting

confidence: 65%

Novel therapies in development for the treatment of traumatic brain injury

Vink

Nimmo

2002

Expert Opinion on Investigational Drugs

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In industrialised countries, the mean per capita incidence of traumatic brain injury (TBI) that results in a hospital presentation is 250 per 100,000. In Europe and North America alone, this translates to > 2 million TBI presentations annually. Approximately 25% of these presentations are admitted for hospitalisation. Despite the significance of these figures, there is no single interventional pharmacotherapy that has shown efficacy in the treatment of clinical TBI. This lack of efficacy in clinical trials may be due, in part, to the inherent heterogeneity of the traumatic brain injury population. However, it is the multifactorial nature of secondary injury that also poses a major hurdle, particularly for those therapies that have been designed to specifically target an individual injury factor. It is now becoming increasingly recognised that any successful TBI therapy may have to simultaneously affect multiple injury factors, somewhat analogous to other broad spectrum interventions. Recent efforts in experimental TBI have therefore focussed on developing novel pharmacotherapies that may affect multiple injury factors and thus improve the likelihood of a successful outcome. While a number of interventions are noteworthy in this regard, this review will focus on three novel compounds that show particular promise: magnesium, substance P antagonists and cyclosporin A.

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Section: Substance P Antagonistssupporting

confidence: 65%

Novel therapies in development for the treatment of traumatic brain injury

Vink

Nimmo

2002

Expert Opinion on Investigational Drugs

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“…These include temporal lobe epilepsy, sclerosis of the temporal lobe, and tumors of the temporal lobe, hypothalamus and other limbic structures. At a pre-clinical level, defensive rage in cats has been proposed to be mediated by a glutamatergic neurotransmitter pathway from the amygdala and hypothalamus to the PAG, which in turn leads to an exaggerated response to stimulation (Siegel et al, 1999; Yao et al, 1999). However, these models require further behavioral validation to ascertain the pathological nature of aggression.…”

Section: Animal Models Of Violencementioning

confidence: 99%

Animal violence demystified

Natarajan

Caramaschi

2010

Front. Behav. Neurosci.

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Violence has been observed in humans and animals alike, indicating its evolutionary/biological significance. However, violence in animals has often been confounded with functional forms of aggressive behavior. Currently, violence in animals is identified primarily as either a quantitative behavior (an escalated, pathological and abnormal form of aggression characterized primarily by short attack latencies, and prolonged and frequent harm-oriented conflict behaviors) or a qualitative one (characterized by attack bites aimed at vulnerable parts of the opponent's body and context independent attacks regardless of the environment or the sex and type of the opponent). Identification of an operational definition for violence thus not only helps in understanding its potential differences from adaptive forms of aggression but also in the selection of appropriate animal models for both. We address this issue theoretically by drawing parallels from research on aggression and appeasement in humans and other animals. We also provide empirical evidences for violence in mice selected for high aggression by comparing our findings with other currently available potentially violent rodent models. The following violence-specific features namely (1) Display of low levels of pre-escalatory/ritualistic behaviors. (2) Immediate and escalated offense durations with low withdrawal rates despite the opponent's submissive supine and crouching/defeat postures. (3) Context independent indiscriminate attacks aimed at familiar/unfamiliar females, anaesthetized males and opponents and in neutral environments. (4) Orientation of attack-bites toward vulnerable body parts of the opponent resulting in severe wounding. (5) Low prefrontal serotonin (5-HT) levels upon repeated aggression. (6) Low basal heart rates and hyporesponsive hypothalamus–pituitary–adrenocortical (HPA) axis were identified uniquely in the short attack latency (SAL) mice suggesting a qualitative difference between violence and adaptive aggression in animals.

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“…17,18 Furthermore, it was shown that both the NK1 receptor and its ligand SP are expressed in the amygdala. 19,20 Recent experiments have also shown that exposing rodents to chronic stress increases the transcription of PPTA and elevates levels of SP release in the MeA. 21,22 Significantly, specific addition of antagonists against the SP receptor (NK1) into the MeA was demonstrated to reduce fear and anxiety related behaviour, whereas injection of SP agonists increased this behaviour.…”

Section: Introductionmentioning

confidence: 99%

A remote and highly conserved enhancer supports amygdala specific expression of the gene encoding the anxiogenic neuropeptide substance-P

et al. 2006

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The neuropeptide substance P (SP), encoded by the preprotachykinin-A (PPTA) gene, is expressed in the central and medial amygdaloid nucleus, where it plays a critical role in modulating fear and anxiety related behaviour. Determining the regulatory systems that support PPTA expression in the amygdala may provide important insights into the causes of depression and anxiety related disorders and will provide avenues for the development of novel therapies. In order to identify the tissue specific regulatory element responsible for supporting expression of the PPTA gene in the amygdala, we used long-range comparative genomics in combination with transgenic analysis and immunohistochemistry. By comparing human and chicken genomes, it was possible to detect and characterise a highly conserved long-range enhancer that supported tissue specific expression in SP expressing cells of the medial and central amygdaloid bodies (ECR1; 158.5 kb 5 0 of human PPTA ORF). Further bioinformatic analysis using the TRANSFAC database indicated that the ECR1 element contained multiple and highly conserved consensus binding sequences of transcription factors (TFs) such as MEIS1. The results of immunohistochemical analysis of transgenic lines were consistent with the hypothesis that the MEIS1 TF interacts with and maintains ECR1 activity in the central amygdala in vivo. The discovery of ECR1 and the in vivo functional relationship with MEIS1 inferred by our studies suggests a mechanism to the regulatory systems that control PPTA expression in the amygdala. Uncovering these mechanisms may play an important role in the future development of tissue specific therapies for the treatment of anxiety and depression.

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Neurokinin-1 expression and co-localization with glutamate and GABA in the hypothalamus of the cat

Cited by 23 publications

References 25 publications

Novel therapies in development for the treatment of traumatic brain injury

Novel therapies in development for the treatment of traumatic brain injury

Animal violence demystified

A remote and highly conserved enhancer supports amygdala specific expression of the gene encoding the anxiogenic neuropeptide substance-P

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