Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we demonstrate that embryonic stem cells can be engineered to differentiate into high percentages of serotonergic and dopaminergic neurons. In vitro, these cells release serotonin and dopamine in response to membrane depolarization. Upon engraftment into the medial prefrontal cortex in rats, the homolog of the human anterior cingulate cortex, the cells assumed neuronal morphologies, expressed monoaminergic-specific proteins, and seemed to functionally integrate, as assessed by the upregulation of the immediate-early gene, cfos. Furthermore, the transplanted animals performed in a manner similar to that of animals that received the antidepressant, citalopram, when administered the forced swim test, a validated model of human depression. These results suggest that transplantation of customized stem cells might perhaps be useful in the study treatment of psychiatric disorders.
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PMID:Antidepressant effect of stem cell-derived monoaminergic grafts. 1792 64

The melanin-concentrating hormone (MCH) system is anatomically and functionally interlaced with the mesocorticolimbic dopamine system. Therefore, we investigated whether MCH(1) receptor knockout (KO) mice are more susceptible than wild-type (WT) mice to psychostimulant-induced locomotor stimulation and sensitization, dopamine receptor-mediated phosphorylation events and c-fos expression within the frontal cortex and ventral striatum. MCH(1) receptor KO mice have 20% higher basal locomotor activity, are hypersensitive to the locomotor activating effects of d-amphetamine (1 mg/kg), and develop behavioral sensitization to a regimen of repeated d-amphetamine administration that does not induce sensitization in WT mice. In addition, d-amphetamine-mediated regulation of p44-mitogen activated protein kinase (MAPK) phosphorylation within the frontal cortex was significantly enhanced in MCH(1) receptor KO mice, when compared with WT mice. No significant genotype difference in the effects of d-amphetamine on MAPK phosphorylation events within the ventral striatum, phosphorylation at Ser(897) of the NR1 subunit of the NMDA receptor or Ca(2+) and cyclic AMP response-element binding-protein (CREB) at Ser(133) in the frontal cortex was detected. d-Amphetamine (3 mg/kg) increased c-fos expression within the frontal cortex in MCH(1) receptor KO mice, but not WT mice. There were no d-amphetamine-induced changes in c-fos expression within the ventromedial striatum in KO or WT mice. Overall, MCH(1) receptor KO mice are hypersensitive to the behavioral and molecular effects of the dopaminergic psychostimulant d-amphetamine. Increased frontal cortical MAPK phosphorylation and c-fos expression in MCH(1) receptor KO mice indicates that the MCH(1) receptor may be an important target for treating neuropsychiatric disorders characterized by frontal cortex dysfunction, including depression, attention deficit hyperactivity disorder (ADHD) and schizophrenia.
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PMID:Behavioral and biochemical responses to d-amphetamine in MCH1 receptor knockout mice. 1800 Aug 9

Depression is associated with abnormal neuronal plasticity. AMPA receptors mediate transmission and plasticity at excitatory synapses in a manner which is positively regulated by phosphorylation at Ser831-GluR1, a CaMKII/PKC site, and Ser845-GluR1, a PKA site. Treatment with the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine increases P-Ser845-GluR1 but not P-Ser831-GluR1. Here, it was found that treatment with another antidepressant, tianeptine, increased P-Ser831-GluR1 in the frontal cortex and the CA3 region of hippocampus and P-Ser845-GluR1 in the CA3 region of hippocampus. A receptorome profile detected no affinity for tianeptine at any monaminergic receptors or transporters, confirming an atypical profile for this compound. Behavioural analyses showed that mice bearing point mutations at both Ser831- and Ser845-GluR1, treated with saline, exhibited increased latency to enter the centre of an open field and increased immobility in the tail-suspension test compared to their wild-type counterparts. Chronic tianeptine treatment increased open-field locomotion and reduced immobility in wild-type mice but not in phosphomutant GluR1 mice. P-Ser133-CREB was reduced in the CA3 region of hippocampus in phosphomutant mice, and tianeptine decreased P-Ser133-CREB in this region in wild-type, but not in phosphomutant, mice. Tianeptine increased P-Ser133-CREB in the CA1 region in wild-type mice but not in phosphomutant GluR1 mice. There were higher basal P-Ser133-CREB and c-fos levels in frontal and cingulate cortex in phosphomutant GluR1 mice; these changes in level were counteracted by tianeptine in a GluR1-independent manner. Using phosphorylation assays and phosphomutant GluR1 mice, this study provides evidence that AMPA receptor phosphorylation mediates certain explorative and antidepressant-like actions under basal conditions and following tianeptine treatment.
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PMID:Involvement of AMPA receptor phosphorylation in antidepressant actions with special reference to tianeptine. 1808 78

Several lines of evidence suggest that D-amphetamine (D-AMPH) withdrawal induces a syndrome with symptoms similar to major depressive disorder (MDD). Upregulation of dynorphin (DYN) may underlie the symptoms of MDD and contribute to the negative emotional symptoms associated with psychostimulant withdrawal. Changes in the serotonin transporter (SERT) have also been reported in MDD, and changes in the immediate early gene c-fos have been observed in the context of psychostimulant withdrawal. This study examined the effects of chronic, escalating doses of D-AMPH followed by 24 h of withdrawal on the expression of prodynorphin (PD) and c-fos mRNA in limbic regions of the brain, caudate putamen (CPu), and brainstem and SERT mRNA expression in the dorsal raphe nucleus (DRN). Male Sprague-Dawley rats were treated three times a day for 4 days with escalating doses of D-AMPH (1-10 mg/kg) and sacrificed 24 h after the last injection. Following 24 h of withdrawal, there was an increase in PD and c-fos mRNA expression in the CPu and nucleus accumbens (NAc), and a decrease in PD and c-fos expression in hippocampus and amygdala. SERT mRNA expression was decreased in the DRN, and PD mRNA expression was increased in the adjacent ventrolateral periaqueductal gray (VLPAG) following D-AMPH withdrawal. These data indicate that region-specific changes in PD and c-fos expression occur after withdrawal, while SERT mRNA expression is suppressed, similar to what has been reported in MDD. Alterations in PD, c-fos, and SERT expression could contribute to the depression-like syndrome associated with psychostimulant withdrawal.
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PMID:Differential regulation of prodynophin, c-fos, and serotonin transporter mRNA following withdrawal from a chronic, escalating dose regimen of D-amphetamine. 1911 47

In the present study, the effects of acupuncture on the behavioral and physiological responses induced by chronic mild stress (CMS) were evaluated. Sprague-Dawley rats were exposed to a variety of chronic unpredictable, mild stressors for 8 weeks. The effects of acupuncture on stress-induced anxiety and anhedonia were investigated using the elevated plus maze (EPM) and sucrose intake test. In addition, c-fos expression, as an early neuronal marker in the brain was also examined utilizing Fos-like immunohistochemistry (FLI). CMS rats significantly reduced the consumption of sucrose intake and latency in the open arms of the EPM, and gained body weight more slowly, compared to non-stressed normal rats. Exposure to CMS also significantly increased FLI in the paraventricular nucleus (PVN) of the hypothalamus. Acupuncture stimulation at point PC6 on the pericardium channels (3 min), but not at other point (TE5), restored stress-induced decrease in the latency in the open arms and significantly attenuated FLI in the PVN produced by CMS. Acupuncture stimulation also tended to restore stress-induced decrease in the sucrose intake. The present results demonstrated that acupuncture was effective in restoring CMS-related biochemical and behavioral impairments such as anxiety and anhedonia and that acupuncture point was more effective than non-acupuncture point. These results suggest that acupuncture has a therapeutic effect on chronic stress-related diseases such as depression and anxiety.
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PMID:The effects of acupuncture stimulation at PC6 (Neiguan) on chronic mild stress-induced biochemical and behavioral responses. 1942 67

Recent hypotheses support the idea that disruption of normal neuronal plasticity mechanisms underlies depression and other psychiatric disorders, and that antidepressant treatment may counteract these changes. In a previous report we found that chronic fluoxetine treatment increases the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule involved in neuronal structural plasticity, in the somatosensory cortex. In the present study we intended to find whether, in fact, cell activation and neuronal structural remodeling occur in parallel to changes in the expression of this molecule. Using immunohistochemistry, we found that chronic fluoxetine treatment caused an increase in the expression of the early expression gene c-fos. Golgi staining revealed that this treatment also increased spine density in the principal apical dendrite of pyramidal neurons. These results indicate that, apart from the medial prefrontal cortex or the hippocampus, other cortical regions can respond to chronic antidepressant treatment undergoing neuronal structural plasticity.
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PMID:Effects of chronic fluoxetine treatment on the rat somatosensory cortex: activation and induction of neuronal structural plasticity. 1942 52

DYT1 dystonia is caused by a trinucleotide deletion of GAG (DeltaGAG) in DYT1, which codes for torsinA. A previous epidemiologic study suggested an association of DYT1 DeltaGAG mutation with early-onset recurrent major depression. However, another study reported no significant association with depression, but instead showed an association with anxiety and dystonia. In this study, we analyzed these related behaviors in Dyt1 DeltaGAG heterozygous knock-in mice. The knock-in mice showed a subtle anxiety-like behavior but did not show depression-like behaviors. The mutant mice also displayed normal sensorimotor gating function in a prepulse inhibition test. While normal hippocampus-dependent contextual fear memory and hippocampal CA1 long-term potentiation (LTP) were observed, the knock-in mice exhibited an enhancement in the formation of cued fear memories. Anatomical analysis indicated that the number of c-fos positive cells was significantly increased while the size of the central nucleus of the amygdala (CE) was significantly reduced in the knock-in mice. These results suggest that the Dyt1 DeltaGAG mutation increased the activity of the CE and enhanced the acquisition of the cued fear memory.
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PMID:Increased c-fos expression in the central nucleus of the amygdala and enhancement of cued fear memory in Dyt1 DeltaGAG knock-in mice. 1961 87

The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased kappa-opioid receptor (KOR) gene expression in the brains of WKY rats, combined with studies implicating the KOR in animal models of depression and anxiety, suggests that alterations in the KOR system could have a role in the WKY behavioral phenotype. Here, the effects of KOR antagonists in the forced swim test (FST) were compared with the WKY and the Sprague-Dawley (SD) rat strains. As previously reported, WKY rats showed more immobility behavior than SD rats. The KOR antagonists selectively produced antidepressant-like effects in the WKY rats. By contrast, the antidepressant desipramine reduced immobility in both strains. Brain regions potentially underlying the strain-specific effects of KOR antagonists in the FST were identified using c-fos expression as a marker of neuronal activity. The KOR antagonist nor-binaltorphimine produced differential effects on the number of c-fos-positive profiles in the piriform cortex and nucleus accumbens shell between SD and WKY rats. The piriform cortex and nucleus accumbens also contained higher levels of KOR protein and dynorphin A peptide, respectively, in the WKY strain. In addition, local administration of nor-binaltorphimine directly into the piriform cortex produced antidepressant-like effects in WKY rats further implicating this region in the antidepressant-like response to KOR antagonists. These results support the use of the WKY rat as a model of affective disorders potentially involving KOR overactivity and provide more evidence that KOR antagonists could potentially be used as novel antidepressants.
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PMID:Antidepressant-like effects of kappa-opioid receptor antagonists in Wistar Kyoto rats. 1992 12

Recent findings suggest that the expression of hypothalamic-pituitary-adrenal (HPA) axis stress response adaptation in rats depends on top-down neural control. We therefore examined whether the medial prefrontal cortex (mPFC) modulates expression of stress response habituation. We transiently suppressed (muscimol microinfusion) or stimulated (picrotoxin microinfusion) mPFC neural activity in rats and studied the consequence on the first time response to psychological stress (restraint) or separately on the development and expression of habituation to repeated restraint. We monitored both the hormonal (corticosterone) and neural (forebrain c-fos mRNA) response to stress. Inactivation of the mPFC had no effect on the HPA-axis response to first time restraint, however increased mPFC activity attenuated stress-induced HPA-axis activity. In a three day repeated restraint stress regimen, inactivation of the mPFC on days 1 and 2, but not day 3, prevented the expression of HPA-axis hormone response habituation. In these same rats, the mPFC activity on day 3 interfered with the expression of c-fos mRNA habituation selectively within the mPFC, lateral septum and hypothalamic paraventricular nucleus. In contrast, inactivation of the mPFC only on day 3, or on all 3 days did not interfere with the expression of habituation. We conclude that the mPFC can permit or disrupt expression of HPA-axis stress response habituation, and this control depends on alteration of neural activity within select brain regions. A possible implication of these findings is that the dysregulation of PFC activity associated with depression and post-traumatic stress disorder may contribute to impaired expression of stress-response adaptation and consequently exacerbation of those disorders.
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PMID:Medial prefrontal cortex activity can disrupt the expression of stress response habituation. 2039 7

Many works showed that nerve growth factor (NGF) injected into the brain of animal model emerges potential antidepressant effects. However, this route of administration significantly restricts the application of NGF clinically. Here, we reported that intranasal NGF could provide an alternative to intraventricular injection. The behavioral analysis showed that intranasal administration of NGF reduced the immobility time in forced swimming test (FST) and tail suspension test (TST) in mice. Likewise, intranasal NGF increased the sucrose intake and the locomotor activity in rats after unpredictable chronic mild stress (UCMS). Furthermore, intranasal NGF increased the levels of monoamine neurotransmitters (norepinephrine, dopamine) in the frontal cortex and hippocampus and affected the number of 5-bromodeoxyuridine (BrdU), c-fos and caspase-3 positive neurons in dentate gyrus of hippocampus in rats after UCMS. In summary, intranasal NGF had significant antidepressant effects on animal models of depression and this route of administration may provide a promising way to deliver NGF to brain in a therapeutic perspective.
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PMID:Intranasal administration of nerve growth factor produces antidepressant-like effects in animals. 2052 Nov 2


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