scholarly journals Influence of monosodium glutamate on calretinin immunoreactivity in the dorsal raphe nucleus in adult rats

2019 ◽  
Vol 75 (05) ◽  
pp. 6255-2019
Author(s):  
JADWIGA JAWORSKA-ADAMU ◽  
ALEKSANDRA KRAWCZYK ◽  
KAROL RYCERZ
Keyword(s):  
Light Microscope ◽  
Dorsal Raphe Nucleus ◽  
Monosodium Glutamate ◽  
Subcutaneous Administration ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Male Rats ◽  
Adult Rats ◽  
Old Rats ◽  
Dorsal Raphé

The aim of this study was to investigate changes of calretinin immunoreactivity in neurons and neuropil of the dorsal raphe nucleus (DRN) after subcutaneous administration of monosodium glutamate (MSG) to adult rats. Studies were conducted on 60-day-old male rats. The animals were divided into a control group (C) and two other groups receiving MSG at a dose of 2g/kg b.w. (I) and 4g/kg b.w. (II) subcutaneously for 3 consecutive days. Immunohistochemical peroxydese-antiperoxydase reaction was conducted with the use of a specific anti-calretinin (CR) antibody on brain slides containing DRN of 63-day-old rats. The cells and neuropil were morphologically and morphometrically analysed under the light microscope Olympus BX51. Statistically significant differences were studied with ANOVA and nonparametric Kruskal-Wallis test. In 63-day-old rats, in DRN: dorsal (DRNd), ventral (DRNv) and interfascicular (DRNif) parts, in animals receiving MSG (I and II), there was a decrease in CR- immunoreactivity in neurons and neuropil in comparison to control rats. Only in the ventrolateral part (DRNvl) a few intensively stained CR-immunoreactive cells were demonstrated. Light microscope observations were confirmed by morphometric analyses. In the DRNd and DRNv of rats receiving MSG (I and II) a decrease in average CR-immunoreactive neuron density was shown in comparison to the C group. In the DRNvl part, a statistically significant decrease in the analysed parameter was present only in I group of animals. Conversely, in DRNif no statistically significant differences were shown between studied groups of rats. In the DRN of animals receiving MSG (I and II) a decrease in average digital immunostaining intensity for CR occurred in neurons and neuropil. The obtained results demonstrated a decrease in CR immunostaining intensity level in neurons and neuropil and a decrease in density of studied protein immunoreactive cells under the influence of subcutaneous administration of MSG to adult rats. These results suggest that MSG may cause neuronal death as a result of oxidative stress or it can alter a calretinin conformation in cells after binding to calcium ions.

scholarly journals Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia

2019 ◽  
Author(s):  
Nandkishore Prakash ◽  
Christiana J. Stark ◽  
Maria N. Keisler ◽  
Lily Luo ◽  
Andre Der-Avakian ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Serotonergic System ◽  
Male Rats ◽  
Vulnerability To Stress ◽  
Neurotransmitter Plasticity ◽  
New Treatments ◽  
Dorsal Raphé

ABSTRACTChronic stress induces anhedonia in susceptible, but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in adult male rats using social defeat and intracranial self-stimulation (ICSS), while changes in serotonergic phenotype were investigated using immunohistochemistry and in situ hybridization. Susceptible, but not resilient, rats displayed an increased number of neurons expressing the biosynthetic enzyme for serotonin, tryptophan-hydroxylase-2 (TPH2), in the ventral subnucleus of the dorsal raphe nucleus (DRv). Further, a decrease in the number of DRv glutamatergic neurons was observed in all stressed animals. This neurotransmitter plasticity is dependent on DR activity, as was revealed by chemogenetic manipulation of the central amygdala, a stress-sensitive nucleus that forms a major input to the DR. Activation of amygdalar corticotropin releasing hormone (CRH)+ neurons abolished the increase in DRv TPH2+ neurons and ameliorated stress-induced anhedonia in susceptible animals. These findings show that activation of amygdalar projections induces resilience, and suppresses the gain of serotonergic phenotype in the DR that is characteristic of susceptible animals. This molecular signature of vulnerability to stress-induced anhedonia and the active nature of resilience could be a target of new treatments for stress-related disorders like depression.SIGNIFICANCE STATEMENTDepression and other mental disorders can be induced by chronic or traumatic stressors. However, some individuals are resilient and do not develop depression in response to chronic stress. A complete picture of the molecular differences between susceptible and resilient individuals is necessary to understand how plasticity of limbic circuits is associated with the pathophysiology of stress-related disorders. Using a rodent model, our study identifies a novel molecular marker of susceptibility to stress-induced anhedonia, a core symptom of depression, and a means to modulate it. These findings will guide further investigation into cellular and circuit mechanisms of resilience, and the development of new treatments for depression.

Enhanced responsiveness to hypoxic panicogenic challenge in female rats in late diestrus is suppressed by short-term, low-dose fluoxetine: Involvement of the dorsal raphe nucleus and the dorsal periaqueductal gray

2021 ◽  
Vol 35 (12) ◽  
pp. 1523-1535
Author(s):  
Matheus F Batistela ◽  
Heloísa H Vilela-Costa ◽  
Alana T Frias ◽  
Paloma M Hernandes ◽  
Thelma A Lovick ◽  
...  
Keyword(s):  
Low Dose ◽  
Dorsal Raphe Nucleus ◽  
Acute Hypoxia ◽  
Periaqueductal Gray ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Female Rats ◽  
Male Rats ◽  
Short Term ◽  
Dorsal Raphé

Background: Acute hypoxia, which is panicogenic in humans, also evokes panic-like behavior in male rats. Panic disorder is more common in women and susceptibility increases during the premenstrual phase of the cycle. Aims: We here investigated for the first time the impact of hypoxia on the expression of panic-like escape behavior by female rats and its relationship with the estrous cycle. We also evaluated functional activation of the midbrain panic circuitry in response to this panicogenic stimulus and whether short-term, low-dose fluoxetine treatment inhibits the hyper-responsiveness of females in late diestrus. Methods: Male and female Sprague Dawley rats were exposed to 7% O2. Females in late diestrus were also tested after short-term treatment with fluoxetine (1.75 or 10 mg/kg, i.p.). Brains were harvested and processed for c-Fos and tryptophan hydroxylase immunoreactivity in the periaqueductal gray matter (PAG) and dorsal raphe nucleus (DR). Results: Acute hypoxia evoked escape in both sexes. Overall, females were more responsive than males and this is clearer in late diestrus phase. In both sexes, hypoxia induced functional activation (c-Fos expression) in non-serotonergic cells in the lateral wings of the DR and dorsomedial PAG, which was greater in late diestrus than proestrus (lowest behavioral response to hypoxia). Increased responding in late diestrus (behavioral and cellular levels) was prevented by 1.75, but not 10 mg/kg fluoxetine. Discussion: The response of female rats to acute hypoxia models panic behavior in women. Low-dose fluoxetine administered in the premenstrual phase deserves further attention for management of panic disorders in women.

Effects of pre-training injection of orexin A into dorsal raphe nucleus in passive avoidance acquisition in male rats

2011 ◽  
Vol 71 ◽  
pp. e180
Author(s):  
Arghavan Shafiee Aghdam ◽  
Ensiyeh Piri ◽  
Abdolrahman Sarihi ◽  
Alireza Komaki ◽  
Siamak Shahidi ◽  
...  
Keyword(s):  
Passive Avoidance ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Male Rats ◽  
Avoidance Acquisition ◽  
Orexin A ◽  
Dorsal Raphé

scholarly journals Effects of pre-training injection of orexin A into dorsal raphe nucleus in passive avoidance acquisition on male rats

2012 ◽  
Vol 32 ◽  
pp. 438-442 ◽  
Author(s):  
Arghavan Shafiee Aghdam ◽  
Ensiyeh Piri ◽  
Abdolrahman Sarihi ◽  
Alireza Komaki ◽  
Siamak Shahidi ◽  
...  
Keyword(s):  
Passive Avoidance ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Male Rats ◽  
Avoidance Acquisition ◽  
Orexin A ◽  
Dorsal Raphé

scholarly journals Baixiangdan Capsule and Shuyu Capsule Regulate Anger-out and Anger-in: GB1 Mediated GABA Can Regulate 5-ht Level in the Dorsal Raphe Nucleus

2021 ◽  
Author(s):  
Xiaoju LIU ◽  
Hai-juan Wang ◽  
Jie Gao ◽  
Xiao-yu Wang ◽  
Yin-xia Ning
Keyword(s):  
Normal Level ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Male Rats ◽  
Abnormal Behavior ◽  
Control Group ◽  
Double Labeling ◽  
Duration Of Action ◽  
Dorsal Raphé

Abstract Background: To explore the intervention mechanism of Baixiangdan Capsule(BXD) and Shuyu Capsule(SY) in the treatment of anger-out and anger-in. A kind of GABABR1(GB1) mediated GABA in the dorsal raphe nucleus(DRN) regulating serotonin(5-HT) levels in the Prefrontal Cortex(PFC), Hippocampus and Hypothalamus in Anger-out and Anger-in male rats. To further explore the difference of Baixiangdan Capsule(BXD) and Shuyu Capsule(SY) in the treatment of anger-out and anger-in.Methods: The anger rat model was established by social isolation combined with resident-intruder paradigm, and behavioral evaluation was used to screen and distinguish anger-out and anger-in model rats. BXD and SY were intervention drugs of anger–out and anger-in rats respectively. On this basis, ELISA was used to detect GABA content in DRN and 5-HT contents in PFC, hippocampus and hypothalamus after different time course (0,1,3,5,7 days) treated with BXD and SY. The co expression of 5-HT and GB1 in DRN was detected by immunofluorescence double labeling technique. Finally, brain stereotactic localization was performed after baclofen, the GB1 specific agonist, and CGP35348, the GB1 specific inhibitor, were injected into the DRN, the 5-HT contents in PFC, hippocampus and hypothalamus was detected by ELISA.Results: After drug treatment, ABT scores and OFT total distance in BXD group were significantly decreased to the level of control group (P<0.05). On the contrary, that in SY group were significantly increased to the level of control group (P<0.05). The sugar water preference coefficient of BXD group and SY group was significantly increased to the normal level (P<0.05). With the increase of the medication duration, 5-HT levels in PFC, hypothalamus and hippocampus increased, gradually corrected its abnormal decline, and returned to the normal level on the 7th day. Besides, GABA level in DRN decreased, gradually corrected its abnormal increase, and also returned to normal level on the 7th day. A large number of 5-HT positive cells (red) in DRN could be seen on immunofluorescence section, and GB1 positive cells (green) could also be seen. Besides, after the drug intervention, 5-HT level in DRN was elevated to normal level (P<0.05). GB1 level in DRN was decreased to normal level in BXD group and SY group (P<0.05). Compared with saline injection, 5-HT levels in PFC, hypothalamus and hippocampus in each group was significantly decreased after injection of baclofen into the DRN (P < 0.05). On the contrary, 5-HT levels in PFC, hypothalamus and hippocampus in each group was significantly increased after the injection of CGP35348 into the DRN.Conclusions: BXD and SY can effectively improve the abnormal behavior changes of anger-out and anger-in rats, and the optimal duration of action is 7 days. The improvement way is to correct the following abnormal changes: The significantly increased GABA in DRN combined with a significantly increased GB1 on 5-HT neurons in DRN, which further mediated the synaptic inhibition effect, thereby reducing 5-HT level of 5-HT neurons in DRN, resulting in a significant decrease of 5-HT levels in PFC, hypothalamus and hippocampus. Therefore, GB1 mediated GABA in DRN can regulate 5-HT levels in PFC, hypothalamus and hippocampus, which may be one of the ways that BXD and SY treat anger-out and anger-in.

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