| 1 | Peptides 2004 Apr 25: 585-8 |
|---|---|
| PMID | 15165713 |
| Title | The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice. |
| Abstract | Bombesin (BN)-like peptides might be involved in the pathogenesis of neuropsychiatric disorders such asschizophrenia. Stereotyped behaviors induced by the dopamine receptor agonist apomorphine or the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine (MK-801) in rodents have been proposed as animal models ofschizophrenicpsychosis. In the present study we evaluated the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801-induced stereotyped behavior in mice. An intraperitoneal (i.p.) injection of RC-3095 (1.0, 10.0 or 100.0 mg/kg) blocked apomorphine-induced stereotypy. The inhibitory effect of RC-3095 on apomorhine-induced stereotypy was similar to that induced by haloperidol (0.5 mg/kg). RC-3095 did not affect stereotyped behavior induced by MK-801 (0.5 mg/kg). The results provide the first evidence that BN/GRPreceptor antagonism blocks stereotyped behavior induced by a dopamine agonist. Together with previous evidence, the present study indicates that the BN/GRPreceptor can be considered a drug target in the investigation of potential new agents for treating neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Peptides 2004 Apr 25: 585-8 |
| PMID | 15165713 |
| Title | The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice. |
| Abstract | Bombesin (BN)-like peptides might be involved in the pathogenesis of neuropsychiatric disorders such asschizophrenia. Stereotyped behaviors induced by the dopamine receptor agonist apomorphine or the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine (MK-801) in rodents have been proposed as animal models ofschizophrenicpsychosis. In the present study we evaluated the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801-induced stereotyped behavior in mice. An intraperitoneal (i.p.) injection of RC-3095 (1.0, 10.0 or 100.0 mg/kg) blocked apomorphine-induced stereotypy. The inhibitory effect of RC-3095 on apomorhine-induced stereotypy was similar to that induced by haloperidol (0.5 mg/kg). RC-3095 did not affect stereotyped behavior induced by MK-801 (0.5 mg/kg). The results provide the first evidence that BN/GRPreceptor antagonism blocks stereotyped behavior induced by a dopamine agonist. Together with previous evidence, the present study indicates that the BN/GRPreceptor can be considered a drug target in the investigation of potential new agents for treating neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | CNS Neurol Disord Drug Targets 2006 Apr 5: 197-204 |
| PMID | 16611092 |
| Title | Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders. |
| Abstract | 哺乳动物蛙皮素(BB)——肽strin-releasing peptide (GRP) stimulates cell proliferation, displays a range of neuroendocrine activities, and acts as a growth factor in the pathogenesis of several types of human cancer. Several lines of evidence have indicated thatGRPand its receptor (GRPR) might also be involved in the neurochemical alterations associated with psychiatric and neurological disorders.GRPandGRPR are distributed throughout the mammalian central nervous system (CNS). Altered levels of BB-like peptides have been found in the CNS of patients withschizophreniaand Parkinson's disease. Dysfunctions inGRPR-induced cellular calcium signaling have been reported in fibroblasts from patients with Alzheimer's disease. A translocation in theGRPR gene has been associated with autism. Pharmacological and genetic studies in rodents have shown thatGRPRs in brain areas such as the dorsal hippocampus and amygdala are importantly involved in regulating synaptic plasticity and aspects of behavior that might be altered in disorders such as anxiety,schizophrenia, depression, autism and dementia. Behaviors modulated by theGRPR in rodents include grooming, food intake, stereotypy, social behavior, and emotionally-motivated learning and memory. Together, these findings support the view that theGRPR should be considered a therapeutic target for a subset of CNS diseases. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Brain Struct Funct 2010 Jun 214: 495-517 |
| PMID | 20512377 |
| Title | The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. |
| Abstract | The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB andGRPsignal satiety. The genes for NMB andGRPare expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted inschizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Stem Cells 2014 Sep 32: 2454-66 |
| PMID | 24806094 |
| Title | Gastrin-releasing peptide contributes to the regulation of adult hippocampal neurogenesis and neuronal development. |
| Abstract | In the postnatal hippocampus, newly generated neurons contribute to learning and memory. Disruptions in neurogenesis and neuronal development have been linked to cognitive impairment and are implicated in a broad variety of neurological and psychiatric disorders. To identify putative factors involved in this process, we examined hippocampal gene expression alterations in mice possessing a heterozygous knockout of the calcium/calmodulin-dependent protein kinase II alpha heterozygous knockout gene (CaMK2?-hKO), an established model of cognitive impairment that also displays altered neurogenesis and neuronal development. Using this approach, we identified gastrin-releasing peptide (GRP) as the most dysregulated gene. In wild-type mice,GRPlabels NeuN-positive neurons, the lone exception beingGRP-positive, NeuN-negative cells in the subgranular zone, suggestingGRPexpression may be relevant to neurogenesis and/or neuronal development. Using a model of in vitro hippocampal neurogenesis, we determined thatGRPsignaling is essential for the continued survival and development of newborn neurons, both of which are blocked by transient knockdown ofGRP's cognate receptor (GRPR). Furthermore,GRPappears to negatively regulate neurogenesis-associated proliferation in neural stem cells both in vitro and in vivo. Intracerebroventricular infusion ofGRPresulted in a decrease in immature neuronal markers, increased cAMP response element-binding protein (CREB) phosphorylation, and decreased neurogenesis. Despite increased levels ofGRPmRNA, CaMK2?-hKO mutant mice expressed reduced levels ofGRPpeptide. This lack ofGRP可能导致神经发生和im升高paired neuronal development, which are reversed following exogenousGRPinfusion. Based on these findings, we hypothesize thatGRPmodulates neurogenesis and neuronal development and may contribute to hippocampus-associated cognitive impairment. |
| SCZ Keywords | schizophrenia, schizophrenic |