Effects of Dietary Fat Profile on Gut Microbiota in Valproate Animal Model of Autism.

Autism spectrum disorder (ASD) is a developmental disability which may cause significant social, communication, and behavioral challenges. Besides certain essential symptoms, a lot of ASD individuals also suffer the comorbidity of gut microbiota dysbiosis, which possibly causes a variety of gastrointestinal (GI) difficulties. Interestingly, evidence has indicated that behavioral output may be modulated through the communication between the central nervous system and gut microbiota via the gut-brain axis. Polyunsaturated fatty acids (PUFAs) and n-3 fatty acids (n-3 PUFA) are structurally and functionally crucial components for the brain, and the state of n-3 PUFAs also affects the gut microbiota. However, how varying intake ratios of n-3/n6 PUFAs affect the gut microbiota composition in ASDs is not well-understood. Pregnant female Wistar rats with intraperitoneal administration of valproate acid (VPA) at embryonic day (E) 12.5 and their male offspring were grouped and fed three diets: a control chow (VPA group), omega-3 deficient (A group), and n-3/n6 (1:5) diet (B group). The diet of pregnant female Wistar rats with intraperitoneal administration of saline and their male offspring was a control chow (normal group). Microbial composition and species abundance were investigated accordingly by the 16S rRNA gene-based metagenomics analysis on the fecal samples. Results showed that fecal microbial abundance was decreased because of VPA administration in the period of pregnancy, and the changing pattern of gut microbiota was similar to that reported in ASD patients. Furthermore, the n-3/n6 (1:5) diet increased the fecal microbial abundance and decreased the elevated Firmicutes. In conclusion, n-3/n6 PUFAs (1:5) diet supplementation may alter gut microbiota composition in VPA-exposed rats. This study put forward a new strategy for the intervention and treatment of autism by n-3/n-6 PUFAs ratio supplementation intakes.

Purulent meningitis caused by Rhodococcus equi: A case report.

RATIONALE: Purulent meningitis refers infection of the subarachnoid space by various purulent bacteria and the corresponding inflammation of the leptomeninges. However, purulent meningitis due to Rhodococcus equi is extremely rare. PATIENT CONCERNS: A 40-year-old man presented with fever and intermittent headache for 6 days. Two hours prior to admission, he developed epileptic seizures. DIAGNOSES: Brain computed tomography and magnetic resonance imaging showed intracerebral malacic lesions. Bacterial culture of cerebrospinal fluid revealed the presence of R. equi. A diagnosis of purulent meningitis caused by R. equi was made. INTERVENTIONS: The patient was treated with intravenous meropenem (1000 mg every 8 hours) for 19 days; then he was discharged and instructed to continue the intravenous meropenem for two weeks. After a follow-up period of 2 months, the patient had recovered completely. OUTCOMES: After a follow-up period of 2 months, the patient had recovered completely. LESSONS: Central nervous system infection caused by R. equi is rare. Early bacterial culture of CSF is important for timely diagnosis. With sufficient antibiotic therapy, the prognosis can be favorable.

Damage to dopaminergic neurons is mediated by proliferating cell nuclear antigen through the p53 pathway under conditions of oxidative stress in a cell model of Parkinson's disease.

Oxidative stress is widely considered as a central event in the pathogenesis of Parkinson's disease (PD). The mechanisms underlying the oxidative damage-mediated loss of dopaminergic neurons in PD are not yet fully understood. Accumulating evidence has indicated that oxidative DNA damage plays a crucial role in programmed neuronal cell death, and is considered to be at least partly responsible for the degeneration of dopaminergic neurons in PD. This process involves a number of signaling cascades and molecular proteins. Proliferating cell nuclear antigen (PCNA) is a pleiotropic protein affecting a wide range of vital cellular processes, including chromatin remodelling, DNA repair and cell cycle control, by interacting with a number of enzymes and regulatory proteins. In the present study, the exposure of PC12 cells to 1-methyl-4-phenylpyridinium (MPP+) led to the loss of cell viability and decreased the expression levels of PCNA in a dose- and time-dependent manner, indicating that this protein may be involved in the neurotoxic actions of MPP+ in dopaminergic neuronal cells. In addition, a significant upregulation in p53 expression was also observed in this cellular model of PD. p53 is an upstream inducer of PCNA and it has been recognized as a key contributor responsible for dopaminergic neuronal cell death in mouse models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. This indicates that MPP+-induced oxidative damage is mediated by the downregulation of PCNA through the p53 pathway in a cellular model of PD. Thus, our results may provide some novel insight into the molecular mechanisms responsible for the development of PD and provide new possible therapeutic targets for the treatment of PD.

Anti-apoptotic effect of microRNA-30b in early phase of rat myocardial ischemia-reperfusion injury model.

This study aimed to investigate the effect of microRNA-30b (miR-30b) in rat myocardial ischemic-reperfusion (I/R) injury model. We randomly divided Sprague-Dawley (SD) rats (n = 80) into five groups: 1) control group; 2) miR-30b group; 3) sham-operated group; 4) I/R group, and 5) I/R+miR-30b group. Real-time quantitative polymerase chain reaction, immunohistochemical staining and Western blot analysis were conducted. TUNEL assay was employed for testing cardiomyocyte apoptosis. Our results showed that miR-30b levels were down-regulated in I/R group and I/R + miR-30b group compared with sham-operated group (both P < 0.05). However, miR-30b level in I/R + miR-30b group was higher than I/R group (P < 0.05). Markedly, the apoptotic rate in I/R group showed highest in I/R group (P < 0.05). Additionally, the results illustrated that protein levels of Bcl-2, Bax, and caspase-3 were at higher levels in ischemic regions in I/R group, comparing to sham-operated group (all P < 0.05), while Bcl-2/Bax was reduced (P < 0.05). Bcl-2 level and Bcl-2/Bax were obviously increased in I/R + miR-30b group by comparison with I/R group, and expression levels of Bax and caspase-3 were down-regulated (all P < 0.05). We also found that in I/R + miR-30b group, KRAS level was apparently lower and p-AKT level was higher by comparing with I/R group (both P < 0.05). Our study indicated that miR-30b overexpression had anti-apoptotic effect on early phase of rat myocardial ischemia injury model through targeting KRAS and activating the Ras/Akt pathway.

The role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness.

Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression.

Lateral habenula as a link between dopaminergic and serotonergic systems contributes to depressive symptoms in Parkinson's disease.

Degeneration of substantia nigra dopaminergic neurons is a key pathological change of Parkinson's disease (PD), and its motor consequences have been widely recognized. Recently, mood disorders associated with PD have begun to attract a great deal of interest, however, their pathogenesis remains unclear. PD is associated with not only degenerative changes in dopaminergic neurons in the substantia nigra but also changes in serotonergic neurons in the raphe nuclei. The abnormalities in central 5-hydroxytryptamine (5-HT) neurotransmission are thought to play a key role in the pathogenesis of depression. The lateral habenula (LHb) is closely related to the substantia nigra and raphe nuclei, and its hyperactivity is closely related to the pathogenesis of depression. In this study, we screened rats with depressive-like behaviors from PD model animals and found that cytochrome c oxidase activity in the LHb of these rats was twice that seen in the control rats. In the forced swim test, LHb lesions caused a decrease in depressive-like behavior of PD rats as indexed by decreased immobility times and increased climbing times. Additionally, LHb lesions caused an enhance in 5-HT levels in the raphe nuclei. These results suggest that LHb lesions may improve depressive-like behavior in PD rats by increasing 5-HT levels in the raphe nuclei. Thus, LHb contributes to the depressive-like behavior in PD rats via mediating the effects of dopaminergic neurons in the substantia nigra on serotonergic neurons in the raphe nuclei.

Flavonoid Myricetin Modulates GABA(A) Receptor Activity through Activation of Ca(2+) Channels and CaMK-II Pathway.

The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABA(A) receptor. This effect of myricetin was not blocked by the GABA(A) receptor benzodiazepine- (BZ-) binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca(2+)/calmodulin-stimulated protein kinase II (CaMK-II). Patch clamp and live Ca(2+) imaging studies found that myricetin could increase Ca(2+) current and intracellular Ca(2+) concentration, respectively, via T- and L-type Ca(2+) channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances GABA(A) receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABA(A) receptor.

Lateral habenula lesions improve the behavioral response in depressed rats via increasing the serotonin level in dorsal raphe nucleus.

The dorsal raphe nucleus (DRN)-serotonin (5-HT) system plays a key role in stress-related psychiatric disorders such as anxiety and depression. The habenular nucleus (Hb) is closely connected with the DRN both morphologically and functionally. Here, we used two types of depressive animal models by exposing rats to chronic mild stress (CMS) and by chronically administering the tricyclic antidepressant clomipramine (CLI) in the rat during the neonatal state of life to produce adult depressed rats. We investigated the effects of lateral habenular nucleus (LHb) lesions on the behavioral response and on the level of 5-HT in DRN in the depressed rats. Forced-swimming test (FST) showed that the immobility time decreased, and the climbing time increased after lesioning LHb of depressed rats. Microdialysis results indicated that the 5-HT level in DRN in depressed rats was lower than that of the control group. Lesion of the LHb was followed by an increased 5-HT turnover in the DRN. Our results suggested that the lesion of the LHb could improve the behavioral response of the depressed rats and the 5-HT level of the DRN increased by LHb lesions could be involved in the effects.